How do cancer cells invade different tissues?
Cancer, a serious health issue, is a major cause of morbidity and mortality worldwide. Although the cancer cells originate at one particular point, they may invade surrounding tissues. Invasion is a process characterized by the extension and penetration of the malignant cells to neighboring tissues. When the cancer cells spread to a different body part from where they originated and grow in other organs, it is called metastasis. Tretament of the cancer becomes challenging when the cancer cells have spread to several parts of the body.
What exactly happens during cancer cells invasion?
Although the cancer cells possess an inherent quality of invading the surrounding tissues, the time and extent of metastasis depend upon genetic factors and extrinsic factors present in that specific microenvironment. Metastasis depends upon decreased adhesion, increased motility and invasion, proteolysis, and resistance to cell death.
Cellular adhesion of the tumor cells with each other and with the basic epithelium where the tumor has grown helps keep the tumor intact. Several chemical regulators and proteins help in maintaining the cell-to-cell adhesion in a tumor. The events that occur during invasion and metastasis can be seen in the following figure 1.
- Developing the invasion potential: When the expression of proteins or chemicals that help keep the tumor intact gets compromised, the cells lose their ability to remain adhered to each other and begin separating from the tumor mass. The loss of cell-cell adhesion also promotes tumor growth.
- Invasion of basement membranes: As the tumors grow in size, the cells leave the original site either as single cells or in groups to further invade other tissues. Collective migration of cancer cells is commonly seen in breast cancer and lung cancer. The type of the tumor matrix and tumor morphology determine the strength with which the matrix holds the cells together and does not allow their migration or detachment. The cells transform their shapes and make their way through the tight holding junctions. This is how they invade the basement membrane of the surrounding tissue.
- Dissociation and invasion: These cells now become mobile and acquire the ability to penetrate surrounding tissues. These cells either alone or in groups enter the lymphatic system or the circulatory system. When the cancer cells invade a single cell, they change their morphology and movement pattern to invade the surrounding tissue. On the other hand, when they invade a group, a whole group of cells detaches and migrates. This is the most common mechanism of invasion. Several genetic expressions play a role in this process. In breast cancer, lymphoma, small cell lung cancer, prostate cancer, and melanoma, invasive growthis commonly seen.
- Intravasation: This also marks the beginning of the angiogenesis process ( developing a new blood vessel network). The tumor needs nutrients to grow, and the blood vessels in its vicinity provide it with a route to enter the blood vessels and migrate. These cells migrate through lymphatic vessels and blood vessels which is termed intravasation. Through the blood or lymph, the cancer cells reach different tissues and organs. For example, breast tumor cells that leave the breast have the potential of entering the lymphatic system.
- Extravasation: The cells now migrate out of the blood vessels and invade secondary sites by entering the tissues known as extravasation. On interacting and adapting with the tissue, they build their vasculature and grow in this secondary site.
- Invasion of secondary tissue: The cells invading the secondary tissue promote further growth of the secondary tumor. Metastasis to the brain is often seen in people having lung, breast, colorectal, and renal
Figure 1: Metastasis cascade.
(Source of figure 1: Jiang WG, et al. Tissue invasion, and metastasis: Molecular, biological and clinical perspectives. Semin Cancer Biol. 2015 Dec;35 Suppl:S244-S275. doi: 10.1016/j.semcancer.2015.03.008. Available at: https://ars.els-cdn.com/content/image/1-s2.0-S1044579X15000231-gr1.jpg)
Conclusively, the invasion of cancer cells is a crucial step in the metastasis of cancer cells. Research shows that the migrating cells are more resistant to chemotherapy. Although cell invasion is a mechanical process, cancer research focuses on gene sequencing and signaling. Targetting treatment towards the invasive pathways of cancer cells could be a new frontier for cancer treatment in the future.
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