Biology of Cancer Chapter 11 1 Cancer o

Biology of Cancer Chapter 11 1

Cancer o o o Derived from Greek word for crab, karkinoma Malignant tumor Tumor n Also referred to as a neoplasm—new growth 2 Mosby items and derived items © 2006 by Mosby, Inc.

Benign vs. Malignant Tumors Benign Grow slowly Malignant Grow rapidly Well-defined capsule Not encapsulated Not invasive Well differentiated Low mitotic index Do not metastasize Invasive Poorly differentiated High mitotic index Can spread distantly (metastasis) 3 Mosby items and derived items © 2006 by Mosby, Inc.

Classification and Nomenclature o Benign tumors n Named according to the tissues from which they arise, and include the suffix “–oma” o o Lipoma Glioma Leiomyoma Chondroma 4 Mosby items and derived items © 2006 by Mosby, Inc.

Classification and Nomenclature o Malignant tumors n Named according to the tissues from which they arise o Malignant epithelial tumors are referred to as carcinomas n o Adenocarcinoma and basal cell carcinoma Malignant connective tissue tumors are referred to as sarcomas n Chondrosarcoma and osteosarcoma 5 Mosby items and derived items © 2006 by Mosby, Inc.

Classification and Nomenclature o o o Cancers of lymphatic tissue are lymphomas Cancers of blood-forming cells are leukemias Carcinoma in situ (CIS) n Pre-invasive epithelial malignant tumors of glandular or epithelial origin that have not broken through the basement membrane or invaded the surrounding stroma 6 Mosby items and derived items © 2006 by Mosby, Inc.

Classification and Nomenclature 7 Mosby items and derived items © 2006 by Mosby, Inc.

Classification and Nomenclature 8 Mosby items and derived items © 2006 by Mosby, Inc.

Cancer Cells o Transformation n n Cancer cell’s independence from normal cellular controls Anchorage independent Immortal Anaplasia o Pleomorphic 9 Mosby items and derived items © 2006 by Mosby, Inc.

Cancer Stem Cells o Stem cells self-renew n o Cell divisions create new stem cells Stem cells are multipotent n Ability to differentiate into multiple different cell types 10 Mosby items and derived items © 2006 by Mosby, Inc.

Cancer Stem Cells 11 Mosby items and derived items © 2006 by Mosby, Inc.

Cancer Stem Cells 12 Mosby items and derived items © 2006 by Mosby, Inc.

Tumor Markers o Tumor cell markers (biological markers) are substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urine n n n Hormones Enzymes Genes Antigens Antibodies 13 Mosby items and derived items © 2006 by Mosby, Inc.

Tumor Markers o Tumor markers are used to: n n n Screen and identify individuals at high risk for cancer Diagnose specific types of tumors Observe clinical course of cancer 14 Mosby items and derived items © 2006 by Mosby, Inc.

Cancer-Causing Mutations o o Cancer is predominantly a disease of aging Clonal proliferation or expansion n Due to a mutation, a cell acquires characteristics that allow it to have selective advantage over its neighbors o o Increased growth rate or decreased apoptosis Multiple mutations are required before cancer can develop 15 Mosby items and derived items © 2006 by Mosby, Inc.

Cancer-Causing Mutations 16 Mosby items and derived items © 2006 by Mosby, Inc.

Types of Mutated Genes o o o o Secretion of growth factors (autocrine stimulation) Increased growth factor receptors Signal from cell-surface receptor is mutated in the “on” position Mutation in the ras intracellular signaling protein Inactivation of Rb tumor suppressor Activation of protein kinases that drive the cell cycle Mutation in the p 53 gene 17 Mosby items and derived items © 2006 by Mosby, Inc.

Types of Mutated Genes 18 Mosby items and derived items © 2006 by Mosby, Inc.

Angiogenesis o o Growth of new vessels Advanced cancers can secrete angiogenic factors 19 Mosby items and derived items © 2006 by Mosby, Inc.

Hallmarks of Cancer 20 Mosby items and derived items © 2006 by Mosby, Inc.

Telomeres and Immorality o o o Body cells are not immortal and can only divide a limited number of times Telomeres are protective caps on each chromosome and are held in place by telomerase Telomeres become smaller and smaller with each cell division 21 Mosby items and derived items © 2006 by Mosby, Inc.

Telomeres and Immorality 22 Mosby items and derived items © 2006 by Mosby, Inc.

Oncogenes and Tumor-Suppressor Genes o Oncogenes n o Tumor-suppressor genes n n o Mutant genes that in their nonmutant state direct protein synthesis and cellular growth Encode proteins that in their normal state negatively regulate proliferation Also referred to as anti-oncogenes Proto-oncogene n A normal, nonmutant gene that codes for cellular growth 23 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation of Normal Genes o Point mutations n o Chromosome translocation n o Changes in one or a few nucleotide base pairs A piece on one chromosome is transferred to another Gene amplification n n Duplication of a small piece of chromosome over and over Results in an increased expression of an oncogene 24 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation of Normal Genes 25 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation of Normal Genes 26 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation of Normal Genes o Mutation of tumor-suppressor genes n o Loss of heterozygosity n o Allows unregulated cellular growth Both chromosome copies of a gene are inactivated Gene silencing n Whole regions of chromosomes are shut off while the same regions in other cells remain active 27 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation of Normal Genes 28 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation of Normal Genes o Caretaker genes n o Encode for proteins that are involved in repairing damaged DNA Chromosome instability n n Increased in malignant cells Results in chromosome loss, loss of heterozygosity, and chromosome amplification 29 Mosby items and derived items © 2006 by Mosby, Inc.

Inflammation and Cancer o Chronic inflammation is an important factor in the development of cancer n n Cytokine release from inflammatory cells Free radicals Mutation promotion Decreased response to DNA damage 30 Mosby items and derived items © 2006 by Mosby, Inc.

Genetics and Cancer o Exposure to mutagens n n If the mutation occurs in somatic cells, it is not passed to progeny If the mutation occurs in germline cells, it can be passed to future generations 31 Mosby items and derived items © 2006 by Mosby, Inc.

Viruses and Cancer o Implicated n n n Hepatitis B and C viruses Epstein-Barr virus (EBV) Kaposi sarcoma herpesvirus (KSHV) Human papillomavirus (HPV) Human T cell leukemia–lymphoma virus (HTLV) 32 Mosby items and derived items © 2006 by Mosby, Inc.

Bacterial Cause of Cancer o Helicobacter pylori n Chronic infections are associated with: o o o Peptic ulcer disease Stomach carcinoma Mucosa-associated lymphoid tissue lymphomas 33 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Tobacco n n Multipotent carcinogenic mixture Linked to cancers of the lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix uteri, and myeloid leukemia 34 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Ionizing radiation n n Emission from x-rays, radioisotopes, and other radioactive sources Exposure causes cell death, gene mutations, and chromosome aberrations Bystander effects Poor gene repair Changes in gap junction intercellular communication 35 Mosby items and derived items © 2006 by Mosby, Inc.

Ionizing Radiation 36 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Ultraviolet radiation n n Causes basal cell carcinoma, squamous cell carcinoma, and melanoma Principal source is sunlight Ultraviolet A (UVA) and ultraviolet B (UVB) Promotes skin inflammation and release of free radicals 37 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Alcohol consumption n n Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver cancers Cigarette/alcohol combination increases a person’s risk 38 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Sexual reproductive behavior n n o Carcinogenic types of human papillomavirus High-risk HPV Physical activity n Reduces cancer risk o o Decreases insulin and insulin-like growth factors Decreases obesity Decreases inflammatory mediators and free radicals Increased gut motility 39 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Occupational hazards n Substantial number of occupational carcinogenic agents o o o Asbestos Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc. Radon 40 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Electromagnetic fields n Carcinogenic? o Are they, or aren’t they? 41 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Diet n Xenobiotics o o o Toxic, mutagenic, and carcinogenic chemicals in food Activated by Phase I activation enzymes Defense mechanisms n o Phase II detoxification enzymes Examples n n Compounds produced in the cooking of fat, meat, or proteins Alkaloids or mold by-products 42 Mosby items and derived items © 2006 by Mosby, Inc.

Environmental Risk Factors o Obesity n n n Correlates with the body mass index (BMI) Adipose tissue is active endocrine and metabolic tissue In response to endocrine and metabolic signaling, adipose tissue releases free fatty acids o o Increased free fatty acids gives rise to insulin resistance and causes chronic hyperinsulinemia Correlates with colon, breast, pancreatic, and endometrial cancers 43 Mosby items and derived items © 2006 by Mosby, Inc.