Tropism between hepatic and pulmonary metastases in colorectal cancers

Kim,Sung-Hyun; Choi,So-Jung; Park,Joon  Suk; Lee,Jinseon; Cho,Yong  Beom; Kang,Min-Woong; Lee,Woo  Yong; Choi,Yong  Soo; Kim,Hong  Kwan; Han,Joungho; Chun,Ho-Kyung; Kim,Jhingook

doi:10.3892/or.2012.1837

Tropism between hepatic and pulmonary metastases in colorectal cancers

Authors:
- Sung-Hyun Kim
- So-Jung Choi
- Joon Suk Park
- Jinseon Lee
- Yong Beom Cho
- Min-Woong Kang
- Woo Yong Lee
- Yong Soo Choi
- Hong Kwan Kim
- Joungho Han
- Ho-Kyung Chun
- Jhingook Kim
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Affiliations: Samsung Biomedical Research Institute, Sungkyunkwan University, School of Medicine, Seoul 135-710, Republic of Korea, Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul 135-710, Republic of Korea, Department of Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul 135-710, Republic of Korea, Department of Thoracic and Cardiovascular Surgery, Chungnam National University, Daejeon 305-764, Chungnam, Republic of Korea, Department of Pathology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul 135-710, Republic of Korea
Published online on: May 29, 2012 https://doi.org/10.3892/or.2012.1837
Pages: 459-464

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Abstract

In metastatic colorectal cancers, tumor cells are disseminated prior to surgical resection of the primary tumor but remain dormant until proper colonization mechanisms are activated. To identify the colonization mechanisms of the metastatic tumors, we conducted a pairwise comparison between primary colorectal cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary pairs. The mRNA levels of 224 genes previously reported to be associated with metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to show consistent expression. Unsupervised hierarchical clustering of the Ct values of metastasis-related genes revealed that liver metastases were indistinguishable from primary colorectal cancers (n=5/6), whereas lung metastases were highly diversified from one another and from the primary tumors (n=6/6). Cytokines and receptor gene expression array data also confirmed the divergence of pulmonary metastases from primary colorectal cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes identified a 17-gene tropism signature that was sufficient not only to distinguish liver and the lung metastases, but also reconstituted the clustering of primary tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary metastases were significantly diverged from hepatic metastases that were indistinguishable from primary colorectal cancers. Further genomic and clinical studies are in progress to evaluate the potential of the tropism signature as a therapeutic target to inhibit the colonization of metastatic colorectal cancers.

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1	Nguyen DX, Paula DB and Massagué J: Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 9:274–284. 2009. View Article : Google Scholar : PubMed/NCBI
2	Fidler IJ: Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 50:6130–6138. 1990.PubMed/NCBI
3	Talmadge JE and Fidler IJ: AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 70:5649–5669. 2010. View Article : Google Scholar : PubMed/NCBI
4	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
5	Pantel K and Brakenhoff RH: Dissecting the metastatic cascade. Nat Rev Cancer. 4:448–456. 2004. View Article : Google Scholar : PubMed/NCBI
6	Braun S, Vogl FD, Naume B, et al: A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 353:793–802. 2005. View Article : Google Scholar : PubMed/NCBI
7	Hüsemann Y, Geigl JB, Schubert F, et al: Systemic spread is an early step in breast cancer. Cancer Cell. 13:58–68. 2008.
8	Lin H, Balic M, Zheng S, Datar R and Cote RJ: Disseminated and circulating tumor cells: Role in effective cancer management. Crit Rev Oncol Hematol. 77:1–11. 2011. View Article : Google Scholar : PubMed/NCBI
9	Flatmark K, Borgen E, Nesland JM, et al: Disseminated tumor cells as a prognostic biomarker in colorectal cancer. Br J Cancer. 104:1434–1439. 2011. View Article : Google Scholar : PubMed/NCBI
10	Sugimura H, Nichols FC, Yang P, et al: Survival after recurrent non small-cell lung cancer after complete pulmonary resection. Ann Thorac Surg. 83:409–418. 2007. View Article : Google Scholar : PubMed/NCBI
11	Feld R, Rubinstein LV and Weisenberger TH: Sites of recurrence in resected stage I non-small-cell lung cancer: a guide for future studies. J Clin Oncol. 2:1352–1358. 1984.PubMed/NCBI
12	Gutt R, Liauw SL and Weichselbaum RR: Adjuvant radiotherapy for resected pancreatic cancer: a lack of benefit or a lack of adequate trials? Nat Clin Pract Gastroenterol Hepatol. 6:38–46. 2009. View Article : Google Scholar : PubMed/NCBI
13	Schabel FM Jr: Rationale for adjuvant chemotherapy. Cancer. 39:2875–2882. 1977. View Article : Google Scholar : PubMed/NCBI
14	Visbal AL, Leighl NB, Feld R and Shepherd FA: Adjuvant chemotherapy for early-stage non-small cell lung cancer. Chest. 128:2933–2943. 2005. View Article : Google Scholar : PubMed/NCBI
15	Navin N, Kendall J, Troge J, et al: Tumour evolution inferred by single-cell sequencing. Nature. 472:90–94. 2011. View Article : Google Scholar : PubMed/NCBI
16	Campbell PJ, Yachida S, Mudie LJ, et al: The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 467:1109–1113. 2010. View Article : Google Scholar : PubMed/NCBI
17	Greaves M and Maley CC: Clonal evolution in cancer. Nature. 481:306–313. 2012. View Article : Google Scholar : PubMed/NCBI
18	Malanchi I, Santamaria-Martinez A, Susanto E, et al: Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 481:85–89. 2011. View Article : Google Scholar : PubMed/NCBI
19	Navab R, Strumpf D, Bandarchi B, et al: Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer. Proc Natl Acad Sci USA. 108:7160–7165. 2011. View Article : Google Scholar : PubMed/NCBI
20	Mink SR, Vashistha S, Zhang W, et al: Cancer-associated fibroblasts derived from EGFR-TKI-resistant tumors reverse EGFR pathway inhibition by EGFR-TKIs. Mol Cancer Res. 8:809–820. 2010. View Article : Google Scholar : PubMed/NCBI
21	Wang W, Li Q, Yamada T, et al: Crosstalk to stromal fibroblasts induces resistance of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors. Clin Cancer Res. 15:6630–6638. 2009. View Article : Google Scholar : PubMed/NCBI
22	Serebriiskii I, Castelló-Cros R, Lamb A, Golemis EA and Cukierman E: Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells. Matrix Biol. 27:573–585. 2008. View Article : Google Scholar : PubMed/NCBI
23	Wilmanns C, Fan D, O’Brian CA, Bucana CD and Fidler IJ: Orthotopic and ectopic organ environments differentially influence the sensitivity of murine colon carcinoma cells to doxorubicin and 5-fluorouracil. Int J Cancer. 52:98–104. 1992. View Article : Google Scholar
24	Kim S-H, Choi S, Cho YB, et al: Differential gene expression during colon-to-lung metastasis. Oncol Rep. 25:629–36. 2011.PubMed/NCBI
25	Gilson N, Honoré O, Detry O, et al: Surgical management of hepatic metastases of colorectal origin. Acta Gastroenterol Belg. 72:321–326. 2009.PubMed/NCBI
26	Kjeldsen BJ, Kronborg O, Fenger C and Jorgensen OD: The pattern of recurrent colorectal cancer in a prospective randomized study and the characteristics of diagnostic tests. Int J Colorectal Dis. 12:329–334. 1997. View Article : Google Scholar : PubMed/NCBI
27	Fidler IJ and Kripke ML: Genomic analysis of primary tumors does not address the prevalence of metastatic cells in the population. Nat Genet. 34:232003. View Article : Google Scholar : PubMed/NCBI
28	Jones S, Chen WD, Parmigiani G, et al: Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci USA. 105:4283–4288. 2008. View Article : Google Scholar : PubMed/NCBI
29	Fidler IJ: The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 3:453–458. 2003.
30	Psaila B and Lyden D: The metastatic niche: adapting the foreign soil. Nat Rev Cancer. 9:285–293. 2009. View Article : Google Scholar : PubMed/NCBI
31	Klein CA: Parallel progression of primary tumours and metastases. Nat Rev Cancer. 9:302–312. 2009. View Article : Google Scholar : PubMed/NCBI
32	Gupta GP and Massague J: Cancer metastasis: building a frame-work. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI
33	Yamamoto J, Sugihara K, Kosuge T, et al: Pathologic support for limited hepatectomy in the treatment of liver metastasis from colorectal cancer. Ann Surg. 221:74–78. 1995. View Article : Google Scholar : PubMed/NCBI
34	Park JS, Kim HK, Choi YS, et al: Outcomes after repeated resection for recurrent pulmonary metastases from colorectal cancer. Ann Oncol. 21:1285–1289. 2010. View Article : Google Scholar : PubMed/NCBI
35	Suriawinata AA and Thung NS: Liver. Histology for Pathologists. Mills SE: 3rd edition. Lippincott Williams & Wilkins; pp. 685–703. 2007
36	Colby TV, Leslie KO and Yousem SA: Lung. Histology for Pathologists. Mills SE: 3rd edition. Lippincott Williams & Wilkins; pp. 473–504. 2007
37	Stelzer G, Inger A, Olender T, et al: GeneDecks: paralog hunting and gene-set distillation with GeneCards annotation. OMICS. 13:477–487. 2009. View Article : Google Scholar : PubMed/NCBI
38	Fidler IJ: Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 50:6130–8. 1990.PubMed/NCBI
39	Kopitz C, Gerg M, Bandapalli OR, et al: Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. Cancer Res. 67:8615–8623. 2007. View Article : Google Scholar : PubMed/NCBI
40	Stein U, Walther W, Arlt F, et al: MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med. 15:59–67. 2009. View Article : Google Scholar : PubMed/NCBI
41	Lee ES, Son DS, Kim S-H, et al: Prediction of recurrence-free survival in postoperative non-small cell lung cancer patients by using an integrated model of clinical information and gene expression. Clin Cancer Res. 14:7397–7404. 2008. View Article : Google Scholar : PubMed/NCBI
42	Koh KH, Rhee H, Kang HJ, et al: Differential gene expression profiles of metastases in paired primary and metastatic colorectal carcinomas. Oncology. 75:92–101. 2008. View Article : Google Scholar : PubMed/NCBI