How cancer, originating in one place spreads throughout our body?

like 907 Posted By : ScienceIndia Administrator

Cancer is a disease of uncontrolled replication, where normal cells are transformed into neoplastic cells. When cancer advances, it spreads to other parts of the body in a process termed as tumor metastasis. Here, the cancer cells break away from the original site, travel through the blood/lymph system to distant sites and form a new tumor in other organs. Metastasis is a major contributor of cancer related deaths. In this process residual tumor cells enter dormancy and evade therapies. It is a complex process involving several morphological and biochemical changes. Interestingly, all the cells in a tumor mass are not capable of metastasis, and not all metastasizing cells are successful in establishing themselves in a secondary site. As you know cells are attached together by various adhering proteins at cell-cell junctions comprising of desmosomes and hemidesmosomes. These are degraded during metastasis and the cells starts detaching itself from the primary tumor. Further, the cells invade through the basement membrane, endothelial cells and either enter the vascular system or the lymphatic system where the cells are now carried to different regions of the body. This step is referred to as ‘intravasation’ and one of the important class of enzymes which facilitates this crucial process are matrix metalloproteases. Once the cells arrive at a suitable secondary site, the process of protease activity is repeated and cells lodge themselves at the organ, a process known as extravasation. Once at the secondary site, the single cell now forms clones of itself to give rise to a secondary tumor mass. This important transformation feature of the cells is often referred to as epithelial to mesenchymal transition (EMT). This is a process wherein cancer cells lose their epithelial morphology of the organ of origin and transform to migratory morphology of mesenchymal phenotype and subsequently acquire epithelial characteristic of the secondary organ after metastasis.

Metastasis is an important characteristic of many cancers because cancer-related deaths are often attributed to this phenomenon. Cells which are highly malignant can metastasize to multiple organs and compromise their functions. Metastasis often occurs in late stages of cancers, where the tumor has gone undetected and untreated, resulting in increased aggressiveness. However, metastasis and secondary tumor formation is a rather complex event, and many scientists believe is a rare occurrence in cancer due to various checkpoints where the process might fail. Cells which do not produce metalloproteases might not enter the circulatory system, and might only metastasize to a site at close proximity to the primary tumor, a phenomenon referred to as ‘micrometastasis’. Cell arising from solid tumors are also anchorage dependent to a basal surface, and hence might not survive and ultimately perish in the circulatory system. There are numerous biological parameters governing the homing of circulating tumor cells (CTCs) to a secondary site, and if conditions are not ideal, the cancer cell might remain in circulation and eventually die. Metastasis may also contribute to relapse in cancer post treatment due to remnant of live cells in secondary tumor site which may not be affected by therapeutic drugs. This makes CTCs a great medium to study disease progression and drug efficacy in cancer and could be used as prognostic and predictive biomarker for monitoring and understanding the metastatic disease.

Article by

Dr. Prashant Kumar

Staff Scientist

 Institute of Bioinformatics, Bangalore, Karnataka

Email: prashant@ibioinformatics.org