Molecular Profiling Predicts the Existence of Two Functionally Distinct Classes of Ovarian Cancer Stroma

Abstract

Although stromal cell signaling has been shown to play a significant role in the progression of many cancers, relatively little is known about its importance in modulating ovarian cancer development. The purpose of this study was to investigate the process of stroma activation in human ovarian cancer by molecular analysis of matched sets of cancer and surrounding stroma tissues. RNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133 Plus 2.0) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of ovarian cancer patients (Cepi) and matched sets of surrounding cancer stroma (CS). For controls, ovarian surface epithelial cells (OSE) were isolated from the normal (noncancerous) ovaries and normal stroma (NS). Hierarchical clustering of the microarray data resulted in clear separations between the OSE, Cepi, NS, and CS samples. Expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples indicate the existence of two subgroups of cancer stroma (CS) with different propensities to support tumor growth. Our results indicate that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development.

Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

“…Recently, one study aimed to investigate the molecular changes in OC stroma compared with normal matched tissue. Microarray profiling found significant differences between normal and cancer-associated stroma, as well as two distinct subgroups of cancer-associated stroma: one with similar receptor/ligand expression to the cancer and one different [34]. They indicated that these might be more permissive or resistant to cancer growth and chemoresistance; however, there has been no follow-up on their profiling data to date.…”

The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

“…Depending on its composition, the stroma can either impede the neoplastic growth or create the conditions for cell growth and cell migration of cancer cells. Although differing from that in normal ovary tissue, the stroma in ovarian cancer may vary in the expression of genes and production of proteins that ultimately affect tumor growth and invasion . Transcriptome profiling of genes encoding signaling molecules and cognate receptors in ovarian cancer cells and matched stromal cells isolated from patients revealed the existence of two distinct stromal compartments, one permissive and one less prone to support cancer growth .…”

“…Although differing from that in normal ovary tissue, the stroma in ovarian cancer may vary in the expression of genes and production of proteins that ultimately affect tumor growth and invasion. 32 Transcriptome profiling of genes encoding signaling molecules and cognate receptors in ovarian cancer cells and matched stromal cells isolated from patients revealed the existence of two distinct stromal compartments, one permissive and one less prone to support cancer growth. 32 Noteworthy, the former was associated with grade 3 and the latter with grade 2 ovarian serous adenocarcinomas.…”

“…32 Transcriptome profiling of genes encoding signaling molecules and cognate receptors in ovarian cancer cells and matched stromal cells isolated from patients revealed the existence of two distinct stromal compartments, one permissive and one less prone to support cancer growth. 32 Noteworthy, the former was associated with grade 3 and the latter with grade 2 ovarian serous adenocarcinomas. 32 Consistent with the above findings, when coinjected with ovarian cancer cells in nude mice, stromal cells isolated from normal ovary were shown to restrict the tumor growth and stromal cells from cancer tissues instead promoted ovarian cancer progression.…”

“…32 Noteworthy, the former was associated with grade 3 and the latter with grade 2 ovarian serous adenocarcinomas. 32 Consistent with the above findings, when coinjected with ovarian cancer cells in nude mice, stromal cells isolated from normal ovary were shown to restrict the tumor growth and stromal cells from cancer tissues instead promoted ovarian cancer progression. 33 A few studies correlate the level of reactive stroma with ovarian cancer progression.…”