Ovarian cancer poses a threat as it frequently remains unnoticed until it metastasizes beyond the ovaries, with symptoms overlapping other ailments. Aging is linked to heightened ovarian cancer spread, yet the precise mechanisms are unclear.
Senescence facilitates spread of ovarian cancer cells
A study by Indian Institute of Science reveals that senescent or aged tissues facilitate easier ovarian cancer cell dispersion due to their secretion of a distinctive extracellular matrix, attracting cancer cells. In their study, researchers employed a chemotherapy-induced senescent model, utilizing mouse-derived tissues from body cavities. Half of the tissues were subjected to cancer-treating chemotherapeutics, inducing senescence—a state where cells cease replication without perishing.
Ramray Bhat, an Associate Professor at the Department of Developmental Biology and Genetics and corresponding author of the study indicates that what is popularly known as body aging in tissue or cells it can be called senescence.
In a study published in Cellular and Molecular Life Sciences, the team exposed mouse tissues and human cell sheets to ovarian cancer cells, using time-lapse imaging with fluorescent markers for microscopic observation over extended periods.
Bharat Thapa, the primary author of the study and former biology undergraduate at IISc clarified that imaging tissues poses greater difficulty than cell lines due to the latter’s homogeneous single-cell type growth.
Cancer cells settle on aged tissues
Researchers discovered that cancer cells preferentially settle on aged tissues, particularly near aged normal cells in cell sheets. Contrary to expectations, computer models revealed it’s not diffusing signaling molecules, but proteins forming the extracellular matrix (ECM) secreted by aged cells that attract cancer cells, facilitating stronger attachment and faster spread.
Also researchers conducted experiments on human cell lines to validate computer simulations and observed cancer cells sticking strongly to the extracellular matrix around aged cells, leading to the clearance of aged cells. This insight suggests chemotherapy-induced senescence may worsen outcomes, emphasizing the importance of judicious chemotherapy use in ovarian cancer treatment.
Bhat suggests exploring probes targeting matrix proteins for predicting cancer cell deposition. On the other hand Thapa envisions future research supporting senolytics, drugs eliminating senescent cells, as a combined therapy with chemotherapy for addressing cancer progression.
