The effect of platelet G proteins on platelet extravasation and tumor growth in the murine model of ovarian cancer

Min Soon Cho, Jiasong Li, Ricardo Gonzalez-Delgado, Hani Lee, Matthew Vasquez, Tiancheng He, Yunjie He, Kai Liu, Tomoyuki Sasano, Bernd Nürnberg, Anil K. Sood, Stephen T.C. Wong, Vahid Afshar-Kharghan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We and other investigators have shown that platelets promote metastasis and the growth of tumors. Our rationale for conducting this study is that platelets' prometastatic and progrowth effects depend on a close encounter between platelets and cancer cells. This interaction occurs inside blood vessels with circulating tumor cells and outside blood vessels with cancer cells residing in the tumor parenchyma. Our hypothesis was that platelet extravasation is required for the effect of platelets on tumor growth. Platelets respond to environmental stimuli by activation of G protein-coupled receptors on their surface. We investigated the impact of various platelet G proteins on the growth of ovarian cancer tumors and platelet extravasation. We used mice with platelet-specific deficiency of Gai2 (Gi), Ga13 (G13), or Gaq (Gq) in a syngeneic ovarian cancer model. We measured the total weight of tumor nodules resected from tumor-bearing mice. We developed methods for automated whole-slide image acquisition and unbiased computerized image analysis to quantify extravasated platelets. We compared the number of platelets inside tumor nodules of platelet G protein-deficient tumor-bearing mice. We found that deficiency of Gi and G13, but not Gq, in platelets resulted in smaller tumors compared with those in corresponding littermates. Deficiency of Gi and G13 in platelets reduced the number of extravasated platelets by.90%, but deficiency of Gq did not reduce the number of extravasated platelets significantly. The lack of Gi or G13 in platelets reduced platelet extravasation into the tumor and tumor growth.

Original languageEnglish (US)
Pages (from-to)1947-1951
Number of pages5
JournalBlood Advances
Volume5
Issue number7
DOIs
StatePublished - Apr 1 2021

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'The effect of platelet G proteins on platelet extravasation and tumor growth in the murine model of ovarian cancer'. Together they form a unique fingerprint.

Cite this