MET Expression During Prostate Cancer Progression

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Apr 23

PMID 27105539

Citations 13

Authors

Esther I Verhoef

Kimberley Kolijn

Maria J De Herdt

Berdine van der Steen

A Marije Hoogland

Hein F B M Sleddens

Leendert H J Looijenga

Geert J L H van Leenders

Affiliations

Soon will be listed here.

Abstract

Tyrosine-kinase inhibitors of the hepatocyte growth factor receptor MET are under investigation for the treatment of hormone-refractory prostate cancer (HRPC) metastasis. Analysis of MET protein expression and genetic alterations might contribute to therapeutic stratification of prostate cancer patients. Our objective was to investigate MET on protein, DNA and RNA level in clinical prostate cancer at various stages of progression. Expression of MET was analyzed in hormone-naive primary prostate cancers (N=481), lymph node (N=40) and bone (N=8) metastases, as well as HRPC (N=54) and bone metastases (N=15). MET protein expression was analyzed by immunohistochemistry (D1C2 C-terminal antibody). MET mRNA levels and MET DNA copy numbers were determined by in situ hybridization. None of the hormone-naive primary prostate cancer or lymph node metastases demonstrated MET protein or mRNA expression. In contrast, MET protein was expressed in 12/52 (23%) evaluable HRPC resections. RNA in situ demonstrated cytoplasmic signals in 14/54 (26%) of the HRPC patients, and was associated with MET protein expression (p=0.025, χ2), in absence of MET amplification or polysomy. MET protein expression was present in 7/8 (88%) hormone-naive and 10/15 (67%) HRPC bone metastases, without association of HRPC (p=0.37; χ2), with MET polysomy in 8/13 (61%) evaluable cases. In conclusion, MET was almost exclusively expressed in HRPC and prostate cancer bone metastasis, but was not related to MET amplification or polysomy. Evaluation of MET status could be relevant for therapeutic stratification of late stage prostate cancer.

Citing Articles

Combined Therapy Targeting MET and Pro-HGF Activation Shows Significant Therapeutic Effect Against Liver Metastasis of CRPC.

Kimura S, Iwano S, Akioka T, Kuchimaru T, Kawaguchi M, Fukushima T Int J Mol Sci. 2025; 26(5).

PMID: 40076928 PMC: 11900290. DOI: 10.3390/ijms26052308.

Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies.

Hussein Mer A, Mirzaei Y, Misamogooe F, Bagheri N, Bazyari A, Keshtkaran Z Drug Deliv Transl Res. 2024; 14(11):2963-2988.

PMID: 38597995 DOI: 10.1007/s13346-024-01564-3.

sBioSITe enables sensitive identification of the cell surface proteome through direct enrichment of biotinylated peptides.

Garapati K, Ding H, Charlesworth M, Kim Y, Zenka R, Saraswat M Clin Proteomics. 2023; 20(1):56.

PMID: 38053024 PMC: 10696767. DOI: 10.1186/s12014-023-09445-6.

Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).

Feng K, Liu C, Wang W, Kong P, Tao Z, Liu W Int J Oncol. 2023; 63(5).

PMID: 37732538 PMC: 10609492. DOI: 10.3892/ijo.2023.5575.

Antibody-drug conjugates in lung cancer: dawn of a new era?.

Coleman N, Yap T, Heymach J, Meric-Bernstam F, Le X NPJ Precis Oncol. 2023; 7(1):5.

PMID: 36631624 PMC: 9834242. DOI: 10.1038/s41698-022-00338-9.

References

Liu T, Mendes D, Berkman C . From AR to c-Met: androgen deprivation leads to a signaling pathway switch in prostate cancer cells. Int J Oncol. 2013; 43(4):1125-30. PMC: 3829778. DOI: 10.3892/ijo.2013.2020. View

Ono K, Kamiya S, Akatsu T, Nakamura C, Li M, Amizuka N . Involvement of hepatocyte growth factor in the development of bone metastasis of a mouse mammary cancer cell line, BALB/c-MC. Bone. 2006; 39(1):27-34. DOI: 10.1016/j.bone.2005.12.006. View

Okayama A, Miyagi Y, Oshita F, Ito H, Nakayama H, Nishi M . Identification of Tyrosine-Phosphorylated Proteins Upregulated during Epithelial-Mesenchymal Transition Induced with TGF-β. J Proteome Res. 2015; 14(10):4127-36. DOI: 10.1021/acs.jproteome.5b00082. View

Varkaris A, Corn P, Parikh N, Efstathiou E, Song J, Lee Y . Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer. Clin Cancer Res. 2015; 22(1):107-21. PMC: 4703437. DOI: 10.1158/1078-0432.CCR-15-0235. View

Zarnegar R, Defrances M . Expression of HGF-SF in normal and malignant human tissues. EXS. 1993; 65:181-99. View

Liu C, Park M, Tsao M . Overexpression of c-met proto-oncogene but not epidermal growth factor receptor or c-erbB-2 in primary human colorectal carcinomas. Oncogene. 1992; 7(1):181-5. View

van Leenders G, van Balken B, Aalders T, Hulsbergen-van de Kaa C, Ruiter D, Schalken J . Intermediate cells in normal and malignant prostate epithelium express c-MET: implications for prostate cancer invasion. Prostate. 2002; 51(2):98-107. DOI: 10.1002/pros.10073. View

Chu G, Zhau H, Wang R, Rogatko A, Feng X, Zayzafoon M . RANK- and c-Met-mediated signal network promotes prostate cancer metastatic colonization. Endocr Relat Cancer. 2014; 21(2):311-26. PMC: 3959765. DOI: 10.1530/ERC-13-0548. View

Kolijn K, Verhoef E, van Leenders G . Morphological and immunohistochemical identification of epithelial-to-mesenchymal transition in clinical prostate cancer. Oncotarget. 2015; 6(27):24488-98. PMC: 4695200. DOI: 10.18632/oncotarget.4177. View

10.

Smith M, Sweeney C, Corn P, Rathkopf D, Smith D, Hussain M . Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study. J Clin Oncol. 2014; 32(30):3391-9. PMC: 4383838. DOI: 10.1200/JCO.2013.54.5954. View

11.

Verras M, Lee J, Xue H, Li T, Wang Y, Sun Z . The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Cancer Res. 2007; 67(3):967-75. DOI: 10.1158/0008-5472.CAN-06-3552. View

12.

van Leenders G, Sookhlall R, Teubel W, de Ridder C, Reneman S, Sacchetti A . Activation of c-MET induces a stem-like phenotype in human prostate cancer. PLoS One. 2011; 6(11):e26753. PMC: 3215704. DOI: 10.1371/journal.pone.0026753. View

13.

Wang X, Huang Y, Christie A, Bowden M, Lee G, Kantoff P . Cabozantinib Inhibits Abiraterone's Upregulation of IGFIR Phosphorylation and Enhances Its Anti-Prostate Cancer Activity. Clin Cancer Res. 2015; 21(24):5578-87. DOI: 10.1158/1078-0432.CCR-15-0824. View

14.

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

15.

Elliott B, Hung W, Boag A, Tuck A . The role of hepatocyte growth factor (scatter factor) in epithelial-mesenchymal transition and breast cancer. Can J Physiol Pharmacol. 2002; 80(2):91-102. DOI: 10.1139/y02-010. View

16.

Bladt F, Riethmacher D, Isenmann S, Aguzzi A, Birchmeier C . Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature. 1995; 376(6543):768-71. DOI: 10.1038/376768a0. View

17.

Hoogland A, Jenster G, van Weerden W, Trapman J, van der Kwast T, Roobol M . ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer. Mod Pathol. 2011; 25(3):471-9. DOI: 10.1038/modpathol.2011.176. View

18.

Hurle R, Davies G, Parr C, Mason M, Jenkins S, Kynaston H . Hepatocyte growth factor/scatter factor and prostate cancer: a review. Histol Histopathol. 2005; 20(4):1339-49. DOI: 10.14670/HH-20.1339. View

19.

Lee Y, Lin S, Yu G, Cheng C, Liu B, Liu H . Identification of Bone-Derived Factors Conferring De Novo Therapeutic Resistance in Metastatic Prostate Cancer. Cancer Res. 2015; 75(22):4949-59. PMC: 4651787. DOI: 10.1158/0008-5472.CAN-15-1215. View

20.

van Leenders G, Gage W, Hicks J, van Balken B, Aalders T, Schalken J . Intermediate cells in human prostate epithelium are enriched in proliferative inflammatory atrophy. Am J Pathol. 2003; 162(5):1529-37. PMC: 1851184. DOI: 10.1016/S0002-9440(10)64286-1. View