Cancer cells are self-sufficient

• They promote their own self replication in the absence of the external signals non-cancer cells rely on.

Cancer cells ignore growth suppressors

• This means there’s no time for DNA repair, in part because cancer cells do not pause between the G1 and S phases.

Cancer cells evade apoptosis

• Thus, cells survive despite DNA damage.

Cancer cells are immortal

• They evade the mitotic crisis that results in the death of non-cancer cells.
• Thus, cancer cells continue replication and perpetuate the DNA damage.
• For example, the telomeres of cancer cells do not shorten over time.
  — Telomeres are protective end-caps, that, in normal somatic cells, shorten with each replication. Eventually, they are too short to protect the chromosomal DNA, and the cell dies.
  — However, telomeres are maintained in cancer cells by an enzyme called telomerase. Thus, the telomeres do not shorten and cell death is avoided.

Cancer cells exhibit altered metabolism

• Sometimes called the Warburg effect, this enables them to meet their unique metabolic needs.
  — Cancer cells use aerobic glycolysis to fuel biosynthesis of new organelles; thus, cancer cells are characterized by increased glucose and glutamine consumption.

EXTRACELLULAR EFFECTS

Cancer cells trigger angiogenesis

• Formation of new blood vessels from existing vasculature enables the tumor to meet its nutritional needs.
  — Interestingly, the “angiogenic switch” is triggered by tumors greater than 2 cm; below this threshold, simple diffusion suffices.

Cancer cells invade and metastasize

• This enables them to cross anatomical boundaries. In contrast, the growth of benign tumors is limited by anatomical boundaries.
• Steps:
  • Cancer cells break free from the primary tumor.
  • They invade the extracellular matrix and migrates to a nearby vessel.
  • Then, in a process called intravasation, the cancer cells enter circulation. Be aware that cancer cells can enter blood and/or lymphatic vessels, and that some cancers are more prone to a specific vessel type.
  • Cancer cells travel within the circulation, where they can form an embolus with T lymphocytes and platelets. This aggregation may protect the cancer cells from destruction.
  • Cancer cells can break free from the embolus and exit the vessel, a process called extravasation.
  • In their new environment, the cancer cells can proliferate to form a metastatic tumor; show that this tumor can also develop its own blood supply.
• Be aware that invasion and metastasis are major causes of morbidity and death from cancer.

Cancer cells evade the immune system

• Ensures their own survival.
  — They can downregulate expression of MHC proteins and presentation of antigens on their own cell surfaces. Thus, they “hide” from the immune system.
  — They can also suppress immune cell responses and release immunosuppressive cytokines, which dampens the ability of the immune system to defend the host.