Stromal-epithelial interactions in the progression of ovarian cancer: Influence and source of tumor stromal cells

Jeff A. Parrott, Eric Nilsson, Rachel Mosher, Gregg Magrane, Donna Albertson, Daniel Pinkel, Joe Gray, Michael K. Skinner

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Stromal cells are essential for the progression of many cancers including ovarian tumors. Stromal cell-epithelial cell interactions are important for tumor development, growth, angiogenesis, and metastasis. In the current study, the effects of normal ovarian bovine stromal cells on ovarian tumor progression was investigated. The hypothesis tested is that ovarian stromal cells will alter the onset and progression of ovarian tumors. Conditioned medium from normal bovine ovarian surface stromal cells was found to stimulate the growth of normal ovarian surface epithelium and had no effect on the growth of human tumor cell lines SKOV3 and OCC1. Human ovarian cancer cell lines, SKOV3 and OCC1, were injected subcutaneously into nude mice to examine tumor progression. Tumor growth in the nude mice was dramatically reduced when normal ovarian surface stromal cells were co-injected with SKOV3 or OCC1 cells. Similar results were obtained with normal bovine or human ovarian stromal cells. In contrast, irrelevant testicular stromal cells and epithelial cells had no effect on tumor growth in the nude mouse. Histological examination of these tumors revealed a characteristic stromal cell component adjacent to epithelial cell colonies. Sections of these tumors were hybridized with species specific genomic probes using fluorescence in situ hybridization to identify cell populations. Epithelial cells were shown to be of human origin (i.e. SKOV3 or OCC1), but stromal cells were found to be primarily murine in origin (i.e. host tissue). No detectable bovine cells were observed in the tumors after one week post-injection. Results suggest that stromal cells are an essential component of ovarian tumors. Interestingly, normal ovarian stromal cells had the ability to inhibit tumor growth, but were not able to survive long-term incubation at the tumor site. The developing tumor appears to recruit host (i.e. murine) stromal cells to invade the tumor and support its growth. In summary, normal ovarian stromal cells can inhibit ovarian tumor progression and the developing tumors recruit adjacent host stroma to become 'tumor stroma'. The tumor stroma likely develop an altered phenotype that cooperates with the tumorigenic epithelial cells to help promote the progression of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume175
Issue number1-2
DOIs
StatePublished - Apr 25 2001
Externally publishedYes

Fingerprint

Stromal Cells
Ovarian Neoplasms
Tumors
Neoplasms
Epithelial Cells
Growth
Nude Mice
Cellular Structures
Cells
Conditioned Culture Medium
Tumor Cell Line
Fluorescence In Situ Hybridization
Growth and Development

Keywords

  • Mesenchymal-epithelial
  • Ovarian cancer
  • Ovarian surface epithelium
  • Ovary
  • Stroma
  • Tumor progression

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Stromal-epithelial interactions in the progression of ovarian cancer : Influence and source of tumor stromal cells. / Parrott, Jeff A.; Nilsson, Eric; Mosher, Rachel; Magrane, Gregg; Albertson, Donna; Pinkel, Daniel; Gray, Joe; Skinner, Michael K.

In: Molecular and Cellular Endocrinology, Vol. 175, No. 1-2, 25.04.2001, p. 29-39.

Research output: Contribution to journalArticle

Parrott, Jeff A. ; Nilsson, Eric ; Mosher, Rachel ; Magrane, Gregg ; Albertson, Donna ; Pinkel, Daniel ; Gray, Joe ; Skinner, Michael K. / Stromal-epithelial interactions in the progression of ovarian cancer : Influence and source of tumor stromal cells. In: Molecular and Cellular Endocrinology. 2001 ; Vol. 175, No. 1-2. pp. 29-39.
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AB - Stromal cells are essential for the progression of many cancers including ovarian tumors. Stromal cell-epithelial cell interactions are important for tumor development, growth, angiogenesis, and metastasis. In the current study, the effects of normal ovarian bovine stromal cells on ovarian tumor progression was investigated. The hypothesis tested is that ovarian stromal cells will alter the onset and progression of ovarian tumors. Conditioned medium from normal bovine ovarian surface stromal cells was found to stimulate the growth of normal ovarian surface epithelium and had no effect on the growth of human tumor cell lines SKOV3 and OCC1. Human ovarian cancer cell lines, SKOV3 and OCC1, were injected subcutaneously into nude mice to examine tumor progression. Tumor growth in the nude mice was dramatically reduced when normal ovarian surface stromal cells were co-injected with SKOV3 or OCC1 cells. Similar results were obtained with normal bovine or human ovarian stromal cells. In contrast, irrelevant testicular stromal cells and epithelial cells had no effect on tumor growth in the nude mouse. Histological examination of these tumors revealed a characteristic stromal cell component adjacent to epithelial cell colonies. Sections of these tumors were hybridized with species specific genomic probes using fluorescence in situ hybridization to identify cell populations. Epithelial cells were shown to be of human origin (i.e. SKOV3 or OCC1), but stromal cells were found to be primarily murine in origin (i.e. host tissue). No detectable bovine cells were observed in the tumors after one week post-injection. Results suggest that stromal cells are an essential component of ovarian tumors. Interestingly, normal ovarian stromal cells had the ability to inhibit tumor growth, but were not able to survive long-term incubation at the tumor site. The developing tumor appears to recruit host (i.e. murine) stromal cells to invade the tumor and support its growth. In summary, normal ovarian stromal cells can inhibit ovarian tumor progression and the developing tumors recruit adjacent host stroma to become 'tumor stroma'. The tumor stroma likely develop an altered phenotype that cooperates with the tumorigenic epithelial cells to help promote the progression of ovarian cancer.

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