THE ROLE OF THE NERVOUS SYSTEM IN CANCER METASTASIS

by Shannon Rodriques

St. Xavier's College (Autonomous),

Mumbai, Maharashtra, India.

 

Cancer as a disease is a leading cause of death worldwide. It is a group of diseases that can develop over time and various types of cancers affect the various organs and tissues of the body such as leukemia, prostate cancer, lymphoma, and more. Cancer is a disease that occurs when the cell breaks free from the constraints placed on it during the process of cell division and it undergoes a phenomenon of uncontrolled, uninhibited growth rapidly. Most studies in the field of oncology have always focused on the genetic aspect of cancer which arises due to abnormalities such as mutations and cell-cell interactions. Recent studies in the field of oncology however have begun to shed light on the role of the nervous system as a major contributor to the spread of cancer. The nervous system is known to govern, to superordinate various aspects of the body, and considering that these cancerous cells are not independent entities, the nervous system plays an integral role in its development and metastasis.


Nerve fibers are dispersed throughout the whole body and these nerves are known to release neurotransmitters and other neuropeptides that act on receptors, these neurotransmitters and neuropeptides are also known to bind to receptors on cancerous cells. Behavioral and psychological stresses, depression, and other factors also contribute to the initiation and progression of cancer. The Hypothalamus-Pituitary axis, dopamine, the PNS, dorsal root ganglion are also attributed to playing a role in cancer initiation and progression. Evidence also exists demonstrating the presence of neurons in cancerous structures.

i) nerve fiber innervating vessels in cancer tissues,

ii) the presence of nerves in the cancerous cells as they continue to exist,

iii) nerve endings transform into cancerous tissues, or

iv) play a critical role in cancer progression and initiation.


In the second condition, a lot of pain is experienced and these nerves do not affect the tumor cells. Nerve fibers with abnormal morphologies were also observed proving that these neurons grew along with the abnormal cancer cells. Studies show the process of neurogenesis as rectal cancer cells were cultured along with neuroepithelial cells.

Humoral modulation is a mechanism via which the nervous system modulates the organs of the body and this stands true for the cancerous cells and structures too. Recent studies have provided enough to establish the fact that cancer metastasis is propagated via humoral modulation and through nerve endings. For example, Hergulin β1 and nerve growth factor are key factors in the development of the neural systems, studies prove that these hormones and factors modulate the activities of certain families of proteases that play an essential role in cancer metastasis as the dissemination or separation of cancerous cells from the primary cancerous structure are an important point which determines whether the tumor will be a malignant or metastatic one. Norepinephrine and GABA are also proven to have upregulated the action of such proteases leading to the propagation of cancerous cells in the prostate and nasopharyngeal area.


Nutrients and gases such as oxygen necessities desired by mostly every cell in our body without which the cells would without an iota of doubt die. Blood vessels are the structures through which these essential nutrients and gases are delivered to every tissue in the body. Angiogenesis is the phenomenon of generating new blood vessels. The process of angiogenesis is also vital for cancer metastasis. Vascularization is the phenomenon of increasing the blood vessels present in a particular area when needed especially during stressful conditions. Studies report that chronic stress which leads to an increase in vascularization can influence tumor metastasis. The environment surrounding the cancer cells under its influence can be termed as the tumor microenvironment. These microenvironments are imperative for the process of metastasis as these microenvironments express for receptors that modulate the nervous system. Macrophages present in these microenvironments are modulated by the beta-adrenergic receptors expressed.


Studies demonstrate the existence of a relationship between the neural system and the immune system. This bidirectional relationship has been under the microscope of neurobiologists and immunologists for some time now. Studies show that mood disorders lead to a decrease in immune cells such as cytotoxic T cells, natural killer cells, and other cells that can detect cancer cells. Research has shown that the nervous system regulates the inflammatory response initiated by the nervous system.

Recent studies conducted discovered the role of the bone marrow in cancer metastasis. It was revealed that the bone marrow recruits disseminated cancer cells that are cancer cells that have broken off from the primary cancer cells. It was discovered that the bone marrow plays a critical role in the formation of a niche for cancerous cells, in tumor angiogenesis and microenvironment. Dopamine is a neurotransmitter that modulates the process of recruiting endothelial progenitor cells from bone marrow to the tumor. An important source of tumor microenvironments is stromal cells, which aid in the spread of cancerous cells. Tumor macrophages generated in the bone marrow are guided by the nervous system.


As the area of research in this particular field of oncology, neurobiology and neuroscience are relatively new, treatment for curing or even preventing the metastasis of cancer due to the role of the nervous system is somewhat novel and lacking. One of the ways to prevent cancer metastasis would be to target those specific primary cancer niches present surrounding primary cancerous cells as these niches are also one of the major hurdles present to restrain cancer metastasis. Treatment with medicine that can specifically target areas of cancer spread and inhibit neurons in that area. Inhibitors prevent the binding of growth factors by binding to the receptors themselves or changing the shape of the receptors. Treatment can also aim at localizing phagocytosis and necrosis locally in the area of cancerous structures. Treatment can also include chemicals or peptides that will help phagocytes and other necrotic cells to recognize tumor receptors which would otherwise be evaded as these phagocytes and other necrotic cells cannot recognize cancer cells. Many cancer researchers are now focusing their attention on microbes and their role in preventing cancer as they play a major role in cancer metastasis. Cancer as a disease without an iota of doubt is a very threatening disease and research is being constantly conducted to study, it’s induction, progression, metastasis, regression and so much more.

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