The role of the tumor stroma in ovarian cancer

Abstract

The tumor microenvironment, consisting of stromal myofibroblasts, endothelial cells, and leukocytes, is growingly perceived to be a major contributor to the pathogenesis and disease progression in practically all cancer types. Stromal myofibroblasts produce angiogenic factors, proteases, growth factors, immune response-modulating proteins, anti-apoptotic proteins, and signaling molecules, and express surface receptors and respond to stimuli initiated in the tumor cells to establish a bi-directional communication network in the microenvironment to promote tumor cell invasion and metastasis. Many of these molecules are candidates for targeted therapy and the cancer stroma has been recently regarded as target for biological intervention. This review provides an overview of the biology and clinical role of the stroma in ovarian cancer.

Keywords: metastasis; ovarian carcinoma; prognosis; stromal myofibroblasts; tumor progression.

Figure 1

Localization of mRNA of cancer-associated molecules to the ovarian carcinoma stroma. OC stromal cells express mRNA of the Ets-1 transcription factor (A), laminin receptors (B,C), and the angiogenic factors IL-8 and bFGF (D,E); (F) negative control. Tumor cells express Ets-1, IL-8, and bFGF (NBT-BCIP as chromogen, nuclear fast red as counterstain).

Figure 2

Biologically linked cancer-associated molecules in ovarian carcinoma cells and the tumor stroma. Graphical illustration linking molecules known to have biological association in this cancer, including hyaluronic acid (HA), basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP), urinary-type plasminogen activator, ETS transcription factors, HuR, and HOXA.