CAS PS 332 Lecture Notes - Lecture 13: Natural Killer Cell, Breast Cancer, Perforin
10 views5 pages
Published on 22 May 2019
School
Department
Course
Professor
Lecture 13: 4/9/19
• Cancer
o Group of >100 diseases
o Characterized by presence of new, abnormal cells that multiply and
spread beyond control
• Neoplastic cells – new & nearly unlimited growth that robs the body of nutrients
w/ no beneficial effects
o Benign
▪ Localized; little threat to physical health
o Malignant
▪ Spread to surrounding tissue or other sites
▪ Metastasis – move to other sites via lymph or blood
▪ Do not respond to “normal” controls on cell growth & division
▪ Organ damage; death
• 4 types of malignant growths:
o Carcinoma – cancers of the epithelial tissues
▪ Epithelial tissues – line outside & inner surfaces of body (skin,
stomach lining, mucous membranes, etc.)
▪ Cancers of breast, prostate, colon, lungs, pancreas, skin
▪ Account for 85% of adult cancer cases
o Sarcoma – cancer in connective tissues
▪ Bone, muscle, cartilage
▪ Account for 2% of adult cancer cases
o Lymphoma – cancer of the lymphatic system
▪ Hodgkin’s disease & non-Hodgkin’s lymphoma
o Leukemia – cancer of blood or blood-forming cells
▪ Blood, stem cells, bone marrow
▪ Proliferation of white blood cells in bloodstream & bone marrow >>
damage to immune system
▪ Most common type of pediatric cancer (30%)
• Cancer and the Immune System
o Immune surveillance theory: NK cells & macrophages recognize & kill
cancer cells
▪ Macrophages – Secrete tumor necrosis factor (TNF)
• Necrosis = “starve” tumor by cutting off access to
blood/nutrients
▪ NK Cells >> Inject perforin >> Induce apoptosis
o Cancer >> Breakdown of 2 “control systems” within single cell:
▪ Cell proliferation
• Necessary for normal growth, development, repair
• Oncogene – mutated gene >> inappropriate proliferation
▪ Safeguards against excessive cell growth
• Tumor suppressor genes prevent mutations & repair
damaged DNA
o Stop proliferation >> Allow DNA repair
o Trigger apoptosis
o Factors that accelerate mutations:
▪ Smoking (carcinogens)
▪ Fatty diet
▪ Radiation exposure
▪ Certain viruses (e.g., HPV)
• Accelerate breakdown of control systems
o Is stress related to immunity & cancer?
▪ Animal studies (virus-induced tumors):
• Increased Tumor growth
• Decreased NK cell cytotoxicity
• Increased Angiogenesis
• Increased Circulating glucose
▪ Limited human studies
• Perceived stress >> Impaired NK cell cytotoxicity
o Clinical significance >> Increased cancer risk???
• Stress >> “mutagenesis” (damage to cell DNA)
• Emerging evidence: childhood adversity may impact
cancer development later in life
• Risk Factors
o Risk factors increase a person’s chance of developing cancer, but not
every person with those risk factors will develop cancer
o Inherent
▪ Genetics
• ~5-10% cancers inherited (esp. breast, prostate, ovarian,
colorectal)
• Breast cancer: 95% linked to combination of genetic &
non-genetic risk
• 1st degree relative 2x to 3x increased risk
▪ Age: strongest risk factor
• Increased incidence & mortality
• But, depends on the type of cancer – e.g., bone cancers
most common <20 years old
▪ Race & Ethnicity
• African-Americans – higher cancer incidence and mortality
than all other groups
• Breast cancer: highest incidence in whites, but highest
mortality in African-Americans
o Environmental
▪ Carcinogen
• Cancer-causing agent such as tobacco, ultraviolet
radiation, or an environmental toxin
• Toxic chemicals
o E.g., asbestos, vinyl chloride, arsenic
▪ Radiation
• 1 in 5 Americans will develop skin cancer
• E.g., melanoma – potentially deadly form of cancer within
the melatonin-containing cells of the skin
o Early exposure, thinning of ozone layer, tanning
• High frequency radiation, ionizing radiation, and ultraviolet
radiation are proven carcinogens
o Emotional
▪ Periodic and persistent clinical depression common among cancer
patients (13-40%)
• Linked to higher risk of early death among people with
cancer