Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
January-2017 Volume 37 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2017 Volume 37 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells

  • Authors:
    • Wei Wen
    • Ge Liu
    • Ke Jin
    • Xiang Hu
  • View Affiliations / Copyright

    Affiliations: Medical Department, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Anorectal Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Emergency Department, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Gastrointestinal Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
  • Pages: 115-122
    |
    Published online on: November 9, 2016
       https://doi.org/10.3892/or.2016.5238
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Numerous studies indicate that the interaction between cancer-associated fibroblasts (CAFs) and tumors is manifested in the entire process of colorectal cancer (CRC) cell development, in which TGF-β1 plays a key role and has a significant effect on promoting the activation of CAFs. However, there are few studies on the mechanisms involved in the activation of CAFs by TGF-β1 to produce an influence on tumor cells. TGF-β1 was added to CAFs for further culture, and the expression of α-SMA was significantly enhanced as shown by immunofluorescence assay. Western blot analysis was performed, and the results showed that TGF-β1 promoted expression of PGP9.5 in a time-dependent manner. After siRNA was used to inhibit the expression of Smad2 or Smad3, the TGF-β1-induced PGP9.5 expression in CAFs was obviously suppressed. In addition, TGF-β1 was also found to promote the expression of PGP9.5 through the ERK1/2 and PI3K pathways. CAFs were cultured on the upper layer of a Transwell plate and TGF-β1 was added. Simultaneously, CRC cells were cultured on the lower layer. The biological behaviors of the cancer cells were detected. According to the results, TGF-β1 promoted the proliferation and invasion of CRC cells and inhibited their apoptosis while activating CAFs. This effect was achieved by induction of the expression of PGP9.5. However, when PGP9.5 was inhibited, the impact of TGF-β1 on tumor cells after activation of CAFs was not fully blocked. Therefore, TGF-β1 can promote PGP9.5 expression in CAFs to facilitate the growth of cancer cells. This finding aids in the identification of new targets for treating CRC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Joyce JA and Pollard JW: Microenvironmental regulation of metastasis. Nat Rev Cancer. 9:239–252. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Hanahan D and Coussens LM: Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell. 21:309–322. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Tommelein J, Verset L, Boterberg T, Demetter P, Bracke M and De Wever O: Cancer-associated fibroblasts connect metastasis-promoting communication in colorectal cancer. Front Oncol. 5:632015. View Article : Google Scholar : PubMed/NCBI

5 

Denys H, Derycke L, Hendrix A, Westbroek W, Gheldof A, Narine K, Pauwels P, Gespach C, Bracke M and De Wever O: Differential impact of TGF-beta and EGF on fibroblast differentiation and invasion reciprocally promotes colon cancer cell invasion. Cancer Lett. 266:263–274. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Mishra P, Banerjee D and Ben-Baruch A: Chemokines at the crossroads of tumor-fibroblast interactions that promote malignancy. J Leukoc Biol. 89:31–39. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Céspedes MV, Sevillano M, Nadal C, Jung P, Zhang XH, et al: Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell. 22:571–584. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Hawinkels LJ, Paauwe M, Verspaget HW, Wiercinska E, van der Zon JM, van der Ploeg K, Koelink PJ, Lindeman JH, Mesker W, ten Dijke P, et al: Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts. Oncogene. 33:97–107. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Taguchi A, Kawana K, Tomio K, Yamashita A, Isobe Y, Nagasaka K, Koga K, Inoue T, Nishida H, Kojima S, et al: Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. PLoS One. 9:e896052014. View Article : Google Scholar : PubMed/NCBI

10 

Brentnall TA: Arousal of cancer-associated stromal fibroblasts: Palladin-activated fibroblasts promote tumor invasion. Cell Adhes Migr. 6:488–494. 2012. View Article : Google Scholar

11 

Casey TM, Eneman J, Crocker A, White J, Tessitore J, Stanley M, Harlow S, Bunn JY, Weaver D, Muss H, et al: Cancer associated fibroblasts stimulated by transforming growth factor beta1 (TGF-beta 1) increase invasion rate of tumor cells: A population study. Breast Cancer Res Treat. 110:39–49. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Dawes LJ, Eldred JA, Anderson IK, Sleeman M, Reddan JR, Duncan G and Wormstone IM: TGF beta-induced contraction is not promoted by fibronectin-fibronectin receptor interaction, or alpha SMA expression. Invest Ophthalmol Vis Sci. 49:650–661. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, Richardson A and Weinberg RA: Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA. 101:4966–4971. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Ao M, Williams K, Bhowmick NA and Hayward SW: Transforming growth factor-beta promotes invasion in tumorigenic but not in nontumorigenic human prostatic epithelial cells. Cancer Res. 66:8007–8016. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Mandelker DL, Yamashita K, Tokumaru Y, Mimori K, Howard DL, Tanaka Y, Carvalho AL, Jiang WW, Park HL, Kim MS, et al: PGP9.5 promoter methylation is an independent prognostic factor for esophageal squamous cell carcinoma. Cancer Res. 65:4963–4968. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Lee YM, Lee JY, Kim MJ, Bae HI, Park JY, Kim SG and Kim DS: Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features. Cancer Sci. 97:1205–1210. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Ohta T and Fukuda M: Ubiquitin and breast cancer. Oncogene. 23:2079–2088. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Watanabe T, Kobunai T, Toda E, Kanazawa T, Kazama Y, Tanaka J, Tanaka T, Yamamoto Y, Hata K, Kojima T, et al: Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray. Clin Cancer Res. 13:415–420. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Mizukami H, Shirahata A, Goto T, Sakata M, Saito M, Ishibashi K, Kigawa G, Nemoto H, Sanada Y and Hibi K: PGP9.5 methylation as a marker for metastatic colorectal cancer. Anticancer Res. 28:2697–2700. 2008.PubMed/NCBI

20 

Nakagawa H, Liyanarachchi S, Davuluri RV, Auer H, Martin EW Jr, de la Chapelle A and Frankel WL: Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles. Oncogene. 23:7366–7377. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Derynck R and Zhang YE: Smad-dependent and Smadindependent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Sappino AP, Schürch W and Gabbiani G: Differentiation repertoire of fibroblastic cells: Expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest. 63:144–161. 1990.PubMed/NCBI

23 

Calon A, Tauriello DV and Batlle E: TGF-beta in CAF-mediated tumor growth and metastasis. Semin Cancer Biol. 25:15–22. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Yamazaki T, Hibi K, Takase T, Tezel E, Nakayama H, Kasai Y, Ito K, Akiyama S, Nagasaka T and Nakao A: PGP9.5 as a marker for invasive colorectal cancer. Clin Cancer Res. 8:192–195. 2002.PubMed/NCBI

25 

Akishima-Fukasawa Y, Ino Y, Nakanishi Y, Miura A, Moriya Y, Kondo T, Kanai Y and Hirohashi S: Significance of PGP9.5 expression in cancer-associated fibroblasts for prognosis of colorectal carcinoma. Am J Clin Pathol. 134:71–79. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Kim HJ, Kim YM, Lim S, Nam YK, Jeong J, Kim HJ and Lee KJ: Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis. Oncogene. 28:117–127. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Kabuta T, Mitsui T, Takahashi M, Fujiwara Y, Kabuta C, Konya C, Tsuchiya Y, Hatanaka Y, Uchida K, Hohjoh H, et al: Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation independently of its hydrolase activity. J Biol Chem. 288:12615–12626. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Hussain S, Foreman O, Perkins SL, Witzig TE, Miles RR, van Deursen J and Galardy PJ: The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling. Leukemia. 24:1641–1655. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Bheda A, Yue W, Gullapalli A, Whitehurst C, Liu R, Pagano JS and Shackelford J: Positive reciprocal regulation of ubiquitin C-terminal hydrolase L1 and beta-catenin/TCF signaling. PLoS One. 4:e59552009. View Article : Google Scholar : PubMed/NCBI

30 

Yu J, Tao Q, Cheung KF, Jin H, Poon FF, Wang X, Li H, Cheng YY, Röcken C, Ebert MP, et al: Epigenetic identification of ubiquitin carboxyl-terminal hydrolase L1 as a functional tumor suppressor and biomarker for hepatocellular carcinoma and other digestive tumors. Hepatology. 48:508–518. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Gonzalez-Zubeldia I, Dotor J, Redrado M, Bleau AM, Manrique I, de Aberasturi AL, Villalba M and Calvo A: Co-migration of colon cancer cells and CAFs induced by TGFβ1 enhances liver metastasis. Cell Tissue Res. 359:829–839. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Guido C, Whitaker-Menezes D, Capparelli C, Balliet R, Lin Z, Pestell RG, Howell A, Aquila S, Andò S, Martinez-Outschoorn U, et al: Metabolic reprogramming of cancer-associated fibroblasts by TGF-β drives tumor growth: Connecting TGF-β signaling with ‘Warburg-like’ cancer metabolism and L-lactate production. Cell Cycle. 11:3019–3035. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Yeung TL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, Zaid TM, Ghosh S, Birrer MJ and Mok SC: TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 73:5016–5028. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wen W, Liu G, Jin K and Hu X: TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells. Oncol Rep 37: 115-122, 2017.
APA
Wen, W., Liu, G., Jin, K., & Hu, X. (2017). TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells. Oncology Reports, 37, 115-122. https://doi.org/10.3892/or.2016.5238
MLA
Wen, W., Liu, G., Jin, K., Hu, X."TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells". Oncology Reports 37.1 (2017): 115-122.
Chicago
Wen, W., Liu, G., Jin, K., Hu, X."TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells". Oncology Reports 37, no. 1 (2017): 115-122. https://doi.org/10.3892/or.2016.5238
Copy and paste a formatted citation
x
Spandidos Publications style
Wen W, Liu G, Jin K and Hu X: TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells. Oncol Rep 37: 115-122, 2017.
APA
Wen, W., Liu, G., Jin, K., & Hu, X. (2017). TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells. Oncology Reports, 37, 115-122. https://doi.org/10.3892/or.2016.5238
MLA
Wen, W., Liu, G., Jin, K., Hu, X."TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells". Oncology Reports 37.1 (2017): 115-122.
Chicago
Wen, W., Liu, G., Jin, K., Hu, X."TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells". Oncology Reports 37, no. 1 (2017): 115-122. https://doi.org/10.3892/or.2016.5238
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team