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. 2020 Nov;18(11):2976-2986.
doi: 10.1111/jth.15020. Epub 2020 Aug 24.

The role of the androgen receptor in prostate cancer-induced platelet aggregation and platelet-induced invasion

Jan K Rudzinski  1 , Natasha P Govindasamy  2 , John D Lewis  2 , Paul Jurasz  3   4   5   6
Affiliations
Free article

The role of the androgen receptor in prostate cancer-induced platelet aggregation and platelet-induced invasion

Jan K Rudzinski et al. J Thromb Haemost. 2020 Nov.
Free article

Abstract

Background: Metastatic prostate cancer progresses from a hormone sensitive androgen receptor expressing phenotype to a hormone insensitive androgen receptor-independent subtype with low overall survival. Human platelets contribute to metastasis via tumor cell-induced platelet aggregation, which in part enhances cancer cell invasion. Given the more aggressive nature of hormone insensitive prostate cancer, we hypothesized that androgen receptor-negative prostate cancer cells exhibit higher platelet aggregation potency and invasive response compared to cells with androgen receptor.

Objective: To characterize the role of androgen receptors in prostate cancer-induced platelet aggregation and platelet-induced invasion.

Methods: Tumor cell-induced platelet aggregation experiments were performed with platelets from healthy human donors and benign prostate (RWPE-1) and prostate cancer cell lines positive (LNCaP) and negative for androgen receptor (DU145 and PC3). Immunoblot measured prostate cancer prothrombin. Modified Boyden chamber invasion assays and zymography were performed to assess the effects of platelets on prostate cancer cell invasion and matrix metalloproteinase (MMP) expression, respectively.

Results: Androgen receptor-positive prostate cancer cell lines failed to induce platelet aggregation. However, androgen receptor-inhibited and -negative cell lines all induced platelet aggregation, which was abolished by dabigatran. Androgen receptor-inhibited and -negative cell lines demonstrated greater expression of prothrombin than androgen receptor-positive cells. Platelets enhanced invasion and MMP-2 and -9 expression by androgen receptor-inhibited and negative prostate cancer cells, but not that of the androgen receptor-positive cells.

Conclusions: Androgen receptor loss within prostate cancer results in increased thrombogenicity due to upregulation of prothrombin expression. Reciprocally, platelets enhance invasion of androgen receptor-negative prostate cancer cells via increased MMP expression.

Keywords: androgen; blood platelets; neoplasm metastasis; neoplasms; receptors; thrombin; thrombosis.

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References

REFERENCES

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
    1. Carroll P, Mohler J. NCCN guidelines updates. prostate cancer and prostate cancer early detection. J Natl Comp Cancn Netw. 2018;16:620-623.
    1. Pearlstein E, Salk P, Yogeeswaran G, Karpatkin S. Correlation between spontaneous metastatic potential, platelet-aggregating activity of cell surface extracts, and cell surface sialylation in 10 metastatic-variant derivatives of a rat renal sarcoma cell line. Prod Natl Acad Sci USA. 1980;77:4336-4339.
    1. Radomski MW, Jenkins DS, Holmes L, Moncada S. Human colorectal adenocarinoma cells: differential nitric oxide synthesis determines their ability to aggregate platelets. Cancer Res. 1991;51:6073-6078.
    1. Alonso-Escolano D, Medina C, Cieslik K, et al. Protein kinase C delta mediates platelet-induced breast cancer cell invasion. J Pharmacol Exp Ther. 2006;318:373-380.

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