CD151 is associated with prostate cancer cell invasion and lymphangiogenesis in vivo

Detchokul,Sujitra; Newell,Bradley; Williams,Elizabeth   D.; Frauman,Albert   G.

doi:10.3892/or.2013.2823

CD151 is associated with prostate cancer cell invasion and lymphangiogenesis in vivo

Authors:
- Sujitra Detchokul
- Bradley Newell
- Elizabeth D. Williams
- Albert G. Frauman
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Affiliations: Clinical Pharmacology and Therapeutics Unit, Department of Medicine (Austin Health/Northern Health), The University of Melbourne, Heidelberg, VIC, Australia, Monash Institute of Medical Research, Monash University, Clayton, Melbourne, VIC, Australia
Published online on: October 29, 2013 https://doi.org/10.3892/or.2013.2823
Pages: 241-247

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Abstract

CD151, a member of the tetraspanin family, is associated with regulation of migration of normal and tumour cells via cell surface microdomain formation. CD151 was found in our laboratory to have a prognostic value in prostate cancer and is a promoter of prostate cancer migration and invasion. These roles involve association with integrins on both cell-cell and cell-stroma levels. Furthermore, CD151 plays a role in endothelial cell motility. CD151 expression was examined in three commonly used prostate cancer cell lines. We investigated CD151 expression, angiogenesis (microvessel density; MVD) and lymphangiogenesis (lymphatic vessel density; LVD) in an orthotopic xenograft model of prostate cancer in matched tumours from primary and secondary sites. CD151 was found to be heterogeneously expressed across different prostate cancer cell lines and the levels of CD151 expression were significantly higher in the highly tumorigenic, androgen-insensitive cells PC-3 and DU-145 compared to the androgen-sensitive cell line LNCaP (P<0.05). The majority of in vivo xenografts developed pelvic lymph node metastases. Importantly, primary tumours that developed metastasis had significantly higher CD151 expression and MVD compared to those which did not develop metastasis (P<0.05). We identified, for the first time, that CD151 expression is associated with LVD in prostate cancer. These findings underscore the potential role of CD151 and angiogenesis in the metastatic potential of prostate cancer. CD151 has a prognostic value in this mouse model of prostate cancer and may play a role in lymphangiogenesis. CD151 is likely an important regulator of cancer cell communication with the surrounding microenvironment.

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1	Liu AY, Roudier MP and True LD: Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile. Am J Pathol. 165:1543–1556. 2004. View Article : Google Scholar : PubMed/NCBI
2	Liu AY and True LD: Characterization of prostate cell types by CD cell surface molecules. Am J Pathol. 160:37–43. 2002. View Article : Google Scholar : PubMed/NCBI
3	Liu AY: Differential expression of cell surface molecules in prostate cancer cells. Cancer Res. 60:3429–3434. 2000.PubMed/NCBI
4	Hemler ME: Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol. 6:801–811. 2005. View Article : Google Scholar : PubMed/NCBI
5	Berditchevski F: Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci. 114:4143–4151. 2001.PubMed/NCBI
6	Levy S and Shoham T: Protein-protein interactions in the tetraspanin web. Physiology. 20:218–224. 2005. View Article : Google Scholar : PubMed/NCBI
7	Testa JE, Brooks PC, Lin JM and Quigley JP: Eukaryotic expression cloning with an antimetastatic monoclonal antibody identifies tetraspanin (PETA-3/CD151) as an effector of human tumor cell migration and metastasis. Cancer Res. 59:3812–3820. 1999.
8	Longo N, Yanez-Mo M, Mittelbrunn M, et al: Regulatory role of tetraspanin CD9 in tumor-endothelial cell interaction during transendothelial invasion of melanoma cells. Blood. 98:3717–3726. 2001. View Article : Google Scholar : PubMed/NCBI
9	Nishiuchi R, Sanzen N, Nada S, et al: Potentiation of the ligand-binding activity of integrin α3β1 via association with tetraspanin CD151. Proc Natl Acad Sci USA. 102:1939–1944. 2005.
10	Ang J, Lijovic M, Ashman LK, Kan K and Frauman AG: CD151 protein expression predicts the clinical outcome of low-grade primary prostate cancer better than histologic grading: a new prognostic indicator? Cancer Epidemiol Biomarkers Prev. 13:1717–1721. 2004.
11	Ang J, Fang BL, Ashman LK and Frauman AG: The migration and invasion of human prostate cancer cell lines involves CD151 expression. Oncol Rep. 24:1593–1597. 2010.PubMed/NCBI
12	Sincock PM, Mayrhofer G and Ashman LK: Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: comparison with CD9, CD63 and α5β1 integrins. J Histochem Cytochem. 45:515–525. 1997.PubMed/NCBI
13	Geary SM, Cambareri AC, Sincock PM, Fitter S and Ashman LK: Differential tissue expression of epitopes of the tetraspanin CD151 recognised by monoclonal antibodies. Tissue Antigens. 58:141–153. 2001. View Article : Google Scholar : PubMed/NCBI
14	Bradford MM: Rapid and sensitive method for quantitation of microgram quantities of protein utilizing principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI
15	Zeng Y, Opeskin K, Goad J and Williams ED: Tumor-induced activation of lymphatic endothelial cells via vascular endothelial growth factor receptor-2 is critical for prostate cancer lymphatic metastasis. Cancer Res. 66:9566–9575. 2006. View Article : Google Scholar
16	Tomayko MM and Reynolds CP: Determination of subcutaneous tumor size in a athymic (nude) mice. Cancer Chemother Pharmacol. 24:148–154. 1989. View Article : Google Scholar : PubMed/NCBI
17	Mehta R, Kyshtoobayeva A, Kurosaki T, et al: Independent association of angiogenesis index with outcome in prostate cancer. Clin Cancer Res. 7:81–88. 2001.PubMed/NCBI
18	Wroel T, Mazur G, Dziegiel P, et al: Density of intranodal lymphatics and VEGF-C expression in B-cell lymphoma and reactive lymph nodes. Folia Histochem Cytobiol. 44:43–47. 2006.PubMed/NCBI
19	Weidner N, Semple JP, Welch WR and Folkman J: Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med. 324:1–8. 1991. View Article : Google Scholar : PubMed/NCBI
20	Weidner N, Carroll PR, Flax J, Blumenfeld W and Folkman J: Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol. 143:401–409. 1993.PubMed/NCBI
21	Weidner N: Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 36:169–180. 1995. View Article : Google Scholar : PubMed/NCBI
22	Quaranta V: Motility cues in the tumor microenvironment. Differentiation. 70:590–598. 2002. View Article : Google Scholar : PubMed/NCBI
23	Schmelz M, Cress AE, Scott KM, et al: Different phenotypes in human prostate cancer: α6 or α3 integrin in cell-extracellular adhesion sites. Neoplasia. 4:243–254. 2002.
24	Witkowski CM, Rabinovitz I, Nagle RB, Affinito KS and Cress AE: Characterization of integrin subunits, cellular adhesion and tumorgenicity of 4 human prostate cell-lines. J Cancer Res Clin Oncol. 119:637–644. 1993. View Article : Google Scholar : PubMed/NCBI
25	Yauch RL, Kazarov AR, Desai B, Lee RT and Hemler ME: Direct extracellular contact between integrin α₃β₁ and TM4SF protein CD151. J Biol Chem. 275:9230–9238. 2000.
26	Kazarov AR, Yang X, Stipp CS, Sehgal B and Hemler ME: An extracellular site on tetraspanin CD151 determines α3 and α6 integrin-dependent cellular morphology. J Cell Biol. 158:1299–1309. 2002.PubMed/NCBI
27	Huss WJ, Hanrahan CF, Barrios RJ, Simons JW and Greenberg NM: Angiogenesis and prostate cancer: identification of a molecular progression switch. Cancer Res. 61:2736–2743. 2001.PubMed/NCBI
28	Steiner I, Jung K, Miller K, Stephan C and Erbersdobler A: Expression of endothelial factors in prostate cancer: A possible role of caveolin-1 for tumour progression. Oncol Rep. 27:389–395. 2012.PubMed/NCBI
29	Gray DR, Huss WJ, Yau JM, et al: Short-term human prostate primary xenografts: an in vivo model of human prostate cancer vasculature and angiogenesis. Cancer Res. 64:1712–1721. 2004. View Article : Google Scholar : PubMed/NCBI
30	Sincock PM, Fitter S, Parton RG, Berndt MC, Gamble JR and Ashman LK: PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function. J Cell Sci. 112:833–844. 1999.
31	Takeda Y, Kazarov AR, Butterfield CE, et al: Deletion of tetraspanin CD151 results in decreased pathological angiogenesis in vivo and in vitro. Blood. 109:1524–1532. 2007. View Article : Google Scholar : PubMed/NCBI
32	Wright MD, Geary SM, Fitter S, et al: Characterization of mice lacking the tetraspanin superfamily member CD151. Mol Cell Biol. 24:5978–5988. 2004. View Article : Google Scholar : PubMed/NCBI
33	Zuo HJ, Liu ZX, Liu XC, et al: Assessment of myocardial blood perfusion improved by CD151 in a pig myocardial infarction model. Acta Pharmacol Sin. 30:70–77. 2009. View Article : Google Scholar : PubMed/NCBI
34	Lan RF, Liu ZX, Liu XC, Song YE and Wang DW: CD151 promotes neovascularization and improves blood perfusion in a rat hind-limb ischemia model. J Endovasc Ther. 12:469–478. 2005. View Article : Google Scholar : PubMed/NCBI
35	Zhang XA, Kazarov AR, Yang X, Bontrager AL, Stipp CS and Hemler ME: Function of the tetraspanin CD151-α6β1 integrin complex during cellular morphogenesis. Mol Biol Cell. 13:1–11. 2002.
36	Yáñez-Mó M, Alfranca A, Cabanas C, et al: Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with α3β1 integrin localized at endothelial lateral junctions. J Cell Biol. 141:791–804. 1998.PubMed/NCBI
37	Offersen BV, Borre M and Overgaard J: Immunohistochemical determination of tumor angiogenesis measured by the maximal microvessel density in human prostate cancer. APMIS. 106:463–469. 1998. View Article : Google Scholar
38	Trojan L, Thomas D, Knoll T, Grobholz R, Alken P and Michel MS: Expression of pro-angiogenic growth factors VEGF, EGF and bFGF and their topographical relation to neovascularisation in prostate cancer. Urol Res. 32:97–103. 2004. View Article : Google Scholar : PubMed/NCBI
39	Zhu W and Dahut WL: Tumor angiogenesis as an early marker of long-term prostate cancer mortality. Future Oncol. 6:341–345. 2010. View Article : Google Scholar : PubMed/NCBI
40	Sadej R, Romanska H, Baldwin G, et al: CD151 regulates tumorigenesis by modulating the communication between tumor cells and endothelium. Mol Cancer Res. 7:787–798. 2009. View Article : Google Scholar : PubMed/NCBI
41	Zheng ZZ and Liu ZX: CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation. Acta Pharmacol Sin. 28:66–72. 2007. View Article : Google Scholar : PubMed/NCBI
42	Zuo HJ, Lin JY, Liu ZY, et al: Activation of the ERK signaling pathway is involved in CD151-induced angiogenic effects on the formation of CD151-integrin complexes. Acta Pharmacol Sin. 31:805–812. 2010. View Article : Google Scholar : PubMed/NCBI
43	Mitchell K, Svenson KB, Longmate WM, et al: Suppression of integrin α3β1 in breast cancer cells reduces cyclooxygenase-2 gene expression and inhibits tumorigenesis, invasion, and cross-talk to endothelial cells. Cancer Res. 70:6359–6367. 2010.
44	Wang X, Ferreira AM, Shao Q, Laird DW and Sandig M: β3 integrins facilitate matrix interactions during transendothelial migration of PC3 prostate tumor cells. Prostate. 63:65–80. 2005.
45	Mitchell K, Szekeres C, Milano V, et al: α3β1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3. J Cell Sci. 122:1778–1787. 2009.
46	Dominguez-Jimenez C, Yanez-Mo M, Carreira A, et al: Involvement of α3 integrin/tetraspanins complexes in the angiogenic response induced by angiotensin II. FASEB J. 15:1457–1459. 2001.