Foundations 2 Week 5 part 2

Hyaluronic acid binds to CD44 on tumor cells, promoting invasion.

EGF, FGF, HGF, collagen, MMPs, TGFβ

• Lost or altered in EMT:
• 1.E- cadherin
• 2.a-catenin, b-catenin frequently translocates to nucleus (Wnt)
• 3.Apico-basal polarity
• 4.Circumferential F-actin fibers
• 5.Epithelial cytokeratins
• Gained in EMT?
• 1.N-cadherin
• 2.avb6 integrin
• 3.Intermediate filament protein - Vimentin
• 4.Matrix metalloproteinases secreted, produced
• 5.Fibronectin secretion
• 6.a-smooth muscle actin (myofibroblasts)
• 7.Motility, Invasiveness

• 1: Detachment from the primary mass (epithelial – mesenchymal transition (EMT))
• 2: Invasion through the basement membrane and migration through the extracellular matrix
• 3: Penetration (intravasion) of blood and/or lymphatic vessels
• 4: Survival within the circulation
• 5: Arrest in the distant organ’s microcirculation (capillaries, sinuses or venules)
• 6: Penetration of vessels at the distant site
• 7: Invasion through the distant site’s parenchyma

• Individual cell migration or collective cell migration.
• Can occur through Intravasation (through veins, accompanied by platelets) and extravasation (involves selectin cell adhesion molecules on the tumor and EC, regulated by the microenvironment).

Drugs that have activity in specific phases of cell cycle. Examples: vinca alkaloids work in M-phase, antimetabolites work in S-phase

Drugs that exert a cytotoxic effect throughout the cell cycle Examples: alkylating agents, anthracyclines

• weak carcinogens that don’t require metabolism
• chemotherapy drugs that form DNA adducts are alkyl groups(e.g. CH3-, C2H5-) to DNA’s guanine residues.

• potent carcinogens
• P450-dependent mixed function oxidases
• Includes cigarette smoke, broiled animal fat,smoked meats, and chemical (e.g. vinyl chloride)

• Produced by Aspergillus flavus, P450
• system yields epoxides, TP53gene mutation
• Found on improperly stored grains and peanuts.