The dominance of the microenvironment in breast and ovarian cancer

Abstract

That cancer development is a multistep process, driven in large part by genetic change, is well established. However, it is becoming increasingly clear that, prior to its emergence, the tumorigenic phenotype must overcome the suppressive effects of the surrounding microenvironment. Because the microenvironment is tissue-specific, cancer in each organ must develop unique strategies to overcome these normal epigenetic suppressors. Surprisingly, the induction of glandularity during the earliest stages of ovarian carcinoma development produces a microenvironment that has much in common with the normal mammary gland. This phenotypic convergence may explain why similar genetic and epigenetic changes appear to play a role in breast and ovarian tumor progression.

Figure 1

Phenotypic convergence during breast and ovarian carcinoma development. The normal OSE is not glandular. OSE cells are cohesive and rest on a BM. However, after follicular rupture the cells migrate into the post-ovulatory wound and lay down their own stromal ECM. During the early stages of ovarian carcinoma formation OSE cells acquire a glandular phenotype such that they come to resemble the normal mammary epithelium architecturally. We have termed this phenotypic convergence. In both the breast and ovary, architectural cues in the glandular microenvironment suppress the emergence of the tumorigenic phenotype. These epigenetic effectors include the BM (black deposit around glandular structure) and cell-cell junctions (small black circles between glandular cells).