Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis

Author:

Yeung Tsz-Lun1,Leung Cecilia S.12,Yip Kay-Pong3,Au Yeung Chi Lam1,Wong Stephen T. C.45,Mok Samuel C.12

Affiliation:

1. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas;

2. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas;

3. Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida;

4. Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas;

5. NCI Center for Modeling Cancer Development, Houston Methodist Research Institute, Houston, Texas

Abstract

Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of <30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the “seed-and-soil” hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

Funder

HHS | National Institutes of Health

HHS | National Institutes of Health (NIH)

Cancer Prevention and Research Institute of Texas (CPRIT)

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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