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

Horm Cancer. 2015 Aug;6(4):131-41. doi: 10.1007/s12672-015-0223-4. Epub 2015 May 15.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Estradiol / metabolism*
  • Female
  • Heterografts
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism
  • Mice, Nude
  • Neoplastic Stem Cells / metabolism*
  • Neovascularization, Pathologic / genetics
  • Progesterone / metabolism*
  • Progestins / metabolism

Substances

  • IGFBP1 protein, human
  • Insulin-Like Growth Factor Binding Protein 1
  • Progestins
  • Progesterone
  • Estradiol