Emerging Hallmarks Deregulating cellular energetics Avolding immune destruction

Question

Emerging Hallmarks Deregulating cellular energetics Avolding immune destruction Genome instability and mutation Tumour-promoting inflammation Enabling Characteristics 2. In addition to the "classic" hallmarks, other characteristics (classified as Emerging hallmarks and Enabling characteristics) have been identified in the past 5-10 years. Why do you think it is crucial for cancer cells to implement these characteristics? At what stage(s) in the progression of the disease do you think they are required?

Explanation / Answer

Macrophages ar etype of white blood cells which ar elargely responsible for the clearance and removal of foreign invaders and altered self cells- cancer cells.

Avoiding Immune detection- cancer cells express higher levels of CD47 (transmembrane protein)on their surface , CD47 binds to a protein (sugnal regulatory protein) SIRP alpha on the surface of macrophages, reducing their ability to fight against cancer cells. Avoiding immune system will be required from the initial stages of cancer progression.

Tumor promoting inflammation- Inflammation is process in which the tissues and cells respond to an injury. There are many similarities between cancerous tumor and wound healing. Both involve the growth, survival and migration of cells. Both require new blood vessels. Immune cells gather near a site of injury to secerte growth factors to begin tissue repair, tumors can also surround themselves with immune cells that secreate these same growth factors to promote their uncontrolled cell growth. Tumor promoting inflammation is required when the tumor cells begin to rapidly divide and immgrate.

Genetic instability and mutation are common in cancer cells. Genetic instability can refer to the accumulation of extra copies of DNA or chromosomes, chromosomal translocations, inversions, deletions, single strand breaks or double strand breaks in DNA. Situations of genome instability and mutation are common in cancer cells. Genetic instability can originate due to deficiencies in DNA repair, or due to loss or gain of chromosomes. Losing genetic stability will favor tumor development, because it favors the generation of mutants that can be selected by the enviornment.

Mutations can be caused either by exogeneous agents like tobacco or endogenous agents i.e, metabolically caused. Mutations and genetic instability are inter-dependent and they are likely to occur at the initial stages of cancer development.

For cancer cells undergoing aerobic respiration, glucose gets broken down into pyruvate and then lactic acid, producing only two molecules of ATP. Whereas normal cells undergoing aerobic respiration glucose gets completely broken down into pyruvate which is further processed into carbon dioxide producing 32 molecules of ATP. Although the number of ATP molecules produced per glucose. they are produced at much higher rate.

Cance cells consume more than 20 times as much glucose compared to normal cells but secreate lactic acid instead of breaking it down completely. They also produce many intermediate biosynthetic precursors, these molecules are used for the production of proteins, lipids and DNA which are continously needed by the rapid dividing cells.

Downregulation of cellular regulation occurs during the progression of the cancer cells.

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