Influence of Cancer-Associated Endometrial Stromal Cells on Hormone-Driven Endometrial Tumor Growth

M. J. Pineda, Z. Lu, D. Cao, J. J. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Cancer-associated fibroblasts have been shown to inhibit or stimulate tumor growth depending on stage, grade, and tumor type. It remains unclear, however, the effect of endometrial-cancer-associated fibroblasts on hormone-driven responses in endometrial cancer. In this study, we investigated the effect of normal and cancer-associated stromal cells from patients with and without endometrial cancer on endometrial tumor growth in response to estradiol (E2) and progesterone (P4). Compared to benign endometrial stromal cells, the low-grade and high-grade cancer-associated stromal cells exhibited a blunted hormone response for proliferation as well as IGFBP1 secretion. Additional analysis of the influence of stromal cells on hormone-driven tumor growth was done by mixing stromal cells from benign, low-grade, or high-grade tumors, with Ishikawa cells for subcutaneous tumor formation. The presence of both benign and high-grade cancer-associated stromal cells increased estradiol-driven xenografted tumor growth compared to Ishikawa cells alone. Low-grade cancer-associated stromal cells did not significantly influence hormone-regulated tumor growth. Addition of P4 attenuated tumor growth in Ishikawa + benign or high-grade stromal cells, but not in Ishikawa cells alone or with low-grade stromal cells. Using an angiogenesis focused real-time array TGFA, TGFB2 and TGFBR1 and VEGFC were identified as potential candidates for hormone-influenced growth regulation of tumors in the presence of benign and high-grade stromal cells. In summary, endometrial-cancer-associated cells responded differently to in vitro hormone treatment compared to benign endometrial stromal cells. Additionally, presence of stromal cells differentially influenced hormone-driven xenograft growth in vivo depending on the disease status of the stromal cells.

Original languageEnglish (US)
Pages (from-to)131-141
Number of pages11
JournalHormones and Cancer
Volume6
Issue number4
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

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