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Sustained angiogenesis
To grow beyond a tiny cluster of cells.
Characteristics of sustained angiogenesis
The creation of their own supply lines for oxygen and nutrients, and a means to evacuate waste products and CO2.
T/F: Tumors do not need to develop angiogenic abilities, as it is intrinsic to proliferating cells.
False.
What is tumor angiogenesis?
The formation of new blood vessels from pre-existing blood vessels.
Oxygen and nutrients supplied by the _____ are crucial for cell function and survival.
vasculature
Vascular endothelial growth factor (VEGF) is secreted by which cell types?
Fibroblasts, macrophages, and some tumor cells.
How do tumor cells respond to hypoxia (being deprived of oxygen)?
Increasing VEGF mRNA expression.
The secretion of VEGF in the tumor microenvironment does what?
Stimulates angiogenesis.
Metastasis
The process of tumor cells breaking away from the primary tumor, migrating to a new location, and establishing a new, or secondary tumor, in the new environment.
T/F: Diagnosis of metastatic disease is often fatal.
True.
The steps in the biological cascade of metastasis:
Loss of cellular adhesion
increased motility and invasiveness
entry and survival in the circulation
exit to new tissue
colonization of a distant site
Extracellular Matrix (ECM)
A large network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body.
Stroma
The cells and tissues that support and give structure to organs, glands, or other tissues in the body.
Basement membrane
A thin, dense layer of extracellular matrix that lines most human tissues, forming the supporting structure and scaffolding for epithelial tissue and separating different types of cells, such as nerve cells and muscle cells.
Cadherins
Linked to the actin cytoskeleton by catenins. They are also the strongest cell-cell attachments.
Cell adhesion proteins
Cells adhere to each other and to the ECM through cell-surface proteins called cell adhesion molecules (CAMs)
Tissue invasion
The mechanism by which tumor cells expand into nearby environments.
Intravasation
Invasion into vessels
Circulating Tumor Cells (CTCs)
Once in the blood of a lymphatic vessel, the cancer cell may travel to other areas of the body.
Invasion in the metastasis cascade:
Depends on the release of secreted proteases, which remodel the ECM to generate space for the advance of cancer cells.
T/F: Survival increases if cancer can attach to platelets as an escort because blood is a hostile environment.
True.
T/F: Some tumors make their own protease
True
What protease(s) can tumors make?
MMP-2 and MMP-9
If a tumor cannot make their own protease, they will co-opt ____ cells to induce protease release.
Stromal
T/F: A large amount of circulating tumor cells are successful
False.
Extravasation
When cancer escapes from the lumina of vessels and penetrate into the surrounding tissue.
Micrometastases
Small clumps of disseminated cancer cells…. Some of which are able to expand into clinically detectable masses.
Colonization
The growth of microscopic to macroscopic metastases.
T/F: Colonization represents the most complex and challenging step of the invasion - metastasis cascade
True.
Metastatic inefficiency
The probability of an individual cancer cell successfully completing all of the steps of the invasion-metastasis is very low.
To acquire motility and invasiveness, carcinoma cells must shed many of their____?
Epithelial phenotypes.
T/F: Epithelial-mesenchymal transition (EMT) is reversible
True.