Hasini Effect and Tumor Metastases
Tumor metastasis is the migration and spread of cancerous cells from the tumor to distant sites in the body, resulting in the development of secondary tumours. Tumours that grow and spread aggressively in this manner are designated malignant cancers. When untreated, they can spread throughout the body and disrupt affected organ function.
For metastasis to occur, the cells of a solid tumour must be able to detach from neighboring cells, break through supporting membranes until they reach a lymphatic or blood vessel. Additionally, the tumour cells also must be able to penetrate the basement membrane of the vessel and lodge in the capillary feeding another organ to form a secondary tumor. The cancer cells use enzymes that digest the extracellular matrix through which cancer cells can migrate but also gives rise to many biologically active molecules—some that promote angiogenesis (the formation of new blood vessels) and others that attract additional cells to the site. Cancer cells exhibit enhanced migration as a consequence of cell proliferation, which causes increased cell density as a result of an increase in the secretion of specific soluble proteins. About 90% of cancer deaths are caused when cancer metastasizes.
Hasini Jayatilaka and her team at the Johns Hopkins University observed that when the cells become too densely packed, some would break off and start spreading. At the cellular level, they were able to identify that interleukin 6 (IL-6) and Interleukin 8 (IL-8) are specifically increased with cell density and increase tumor cell migration in a cell density dependent manner. This effect is specific to metastatic cancer cells. Furthermore, IL-6 and IL-8 have no effect on the migration of normal and non-metastatic cancer cells. This discovery offers a significant place for cancer treatment.
Jayatilaka began by studying how cancer cells behave and communicate with each other, using a 3-D model that mimics human tissue. Many researchers believe metastasis happens after the primary tumor reaches a certain size, but Jayatilaka found it was the tumor’s cell density that determined when it would metastasize. Once the cancer cells start to sense the presence of too many other cancer cells around them, they start secreting the Interleukin proteins.
This early communication amongst the cells to move away from the primary cancer and seed metastases has been named “Hasini Effect” in honour of Hasini Jayatilaka originally from Srilanka.
Animal studies have shown that therapeutic targeting of the receptors of IL-6 and IL-8 using certain molecules (drugs) like Tocilizumab and Reparixin significantly decreases metastasis by binding to the Interleukin receptors and block their signals, slowing metastasis.
Cancer is a complex system, not just a disease. Cancer therapy approach should be multipronged surgery to reduce the bulk or eliminate the gross disease,radiation to consolidate the gains of surgery and systemic therapy(chemotherapy/immunotherapy/molecular /genetic therapy) to overcome the challenges that these immortal cells place before us.
Maybe ,with the understanding of the reasons for abnormal cell formation leading to cancer we will learn how to prevent this disease rather than need to treat it!!