Neoplasia: Invasion and Metastasis Flashcards
What is the definition of metastases?
tumors discontinuous with the primary tumor.or the transfer of malignant cells from the primary site to non-connected secondary site
Invasion and metastasis are characteristics of _______
malignant tumors. Benign tumors don’t invade or metastasize.
What are the three mechanisms of metastasis?
- lymphatogenous
- hematogenous
- cavitary
What is the pre-invasive stage and what does it mean?
this is called “carcinoma in situ”. In this stage epithelial cells have all the cytologic features of malignancy, but the cancer hasn’t invaded the basement membrane yet.
What is cavitary dissemination and what is one example?
the cancer breaks away from the original tumor and seeds in body cavities. Eg.-ovarian cancer
what is extravasation?
cancer cells exiting capillaries and entering organs (in the case of metastasis)
What is intravasation?
The invasion of cancer cells through the basal membrane into the blood or a lymph vessel.
What is lymphatogenous dissemination? what is the mechanism?
Intravasation and extravasation occur in the lymph. primary tumor–>lymph node–>other parts of body–>drain into systemic venous system–>can spread hematogenously
what is hematogenous dissemination? what is the mechanism?
Intra and extravasation occur in the blood. primary tumor penetrate blood vessels–>passively transported in the blood vessels to distant sites–> penetrate vessel–>build new tumor
What is the most common route of metastasis for sarcomas?
hematogenous dissemination
What is the most common route of metastasis for carcinomas?
lymphatogenous dissemination
whats the difference between a carcinoma and a sarcoma?
carcinoma arises from epithelial cells, sarcoma arises from mesenchymal cells (like bone)
Malignant tumors still recognize anatomic boundaries T or F?
F
explain some theories about why tumors metastasize
selection pressure- the cells are proliferating faster than they can make vasculature for itself. With increasing size of tumor hypoxia occurs because of limited blood supply and nutrients. Cells want to move out. Thus it is advantageous for primary tumors to metastasize
Increasing tumor size usually correlates with ______ risk of developing metastases.
increased
How does metastasis occur?
carcinoma cells must first invade the ECM by1. breeching the underlying basement membrane2. traversing the interstitial connective tissue3. gaining access to circulation by inravasation (must breech the vascular basement membrane) extravasation is the same in reverse
what does the inflammatory response do to cancer?
it is meant to heal but instead supports tumor growth
Cancer cells have the ability to ______ which allows them to most effectively support neoplastic proliferation.
modify cellular metabolism
modifying cellular metabolism allows cancer cells to evade_____
immunological destruction
What are the 4 steps of invasion (as in intravasation of cancer cells)?
- loosen up cell-cell interactions (i.e. loss of E-cadherin) cells begin to dissociate2. degradation of ECM (basement membrane and interstitial CT)3. attachment to ECM components4. migration of tumor cellsfor extravasation the process is reversed.
What are the four major theories to describe the bias of certain cancers for certain organs?
- metastasis is caused by rare variant clones that develop in the primary tumor.2. metastasis is caused by the gene expression pattern of most cells of the primary tumor (they have a metastatic signature)3. combo of 1 and 2– metastatic variants appear in a tumor with metastatic gene signature4. metastasis is greatly affected by the microenvironment (angiogenesis, local invasiveness, resistance to immune elimination).
epithelial cells are held together by ____
E-cadherin
overexpression of _____ may favor metastatic spread.
CD44
What are the four steps of the metastatic cascade?
- invasion- through the basement membrane and ECM2. Intravasation- getting into a blood or lymph vessel3. extravasation- getting out of a vessel at new site4. Colonization- ability to grow in new site
On the intracellular side what does E-cadherin connect to?
Beta-catenin-alpha-catenin actin complex forms dynamic link to cytoskeleton.
loss of heterozygosity can cause _____
E-cadherin expression to be lost.
SNAIL, SLUG, TWIST, ZEB1/2 are transcriptional repressors that promote _______ by repressing _______.
EMT (epithelial to mesenchymal transition)E-cadherin
How do MMPs regulate tumor invasion?
- remodeling insoluble components of basement membrane2. releasing ECM-sequestered growth factors
Tumor cells can make proteolytic enzymes themselves or induce ______ to make them.
stromal cells
what are MMPs?
proteolytic enzymes. Matrix metalloproteinases
what is ameboid migration?
a 2nd type of invasion that tumor cells can possess which allows them to squeeze through spaces in the ECM instead of cutting through it with proteolytic enzymes like MMP (this is why MMP inhibitors don’t work on cancer).
Lots of adhesion in normal cells leads to _____
apoptosis. Normal cells are resistant to this.
What is a secondary problem of cancer cells modifying the ECM?
it can lead ECM to further promoting invasion and metastasis.
what is anoikis?
death by detachment (happens in normal epithelial cells)
Movement of tumors can be potentiated and directed by what things?
- tumor cell-derived cytokines (autocrine)2. cleavage products of matrix components (collagen, laminin)3. growth factors which have chemotactic activity for tumor cells (IGFI and II)4. Paracrine effectors of cell motility secreted by stromal cells.
Once in circulation, tumor cells are vulnerable to destruction from what?
mechanical shear stress and immune defenses
Tumor overexpression of _____ favors metastatic spread.
CD44
In extravasation tumor emboli adhere to endothelium of distant sites and egress through basement membranes. This involves what molecules?
adhesion molecules, such as integrins, laminin receptors, and proteolytic enzymes.
CD44 adhesion molecule expressed on normal ______ is used by cancer cells to migrate to selective sites in _______
T lymphocyteslymphoid tissue
What are the direct effects of metastasis?
invasive masses directly interfere with normal function.
What are the indirect effects of metastasis?
paraneoplastic syndrome (paracrine, endocrine effects). A disease that involves hormones and cytokines. It is the consequence of cancer but not due to local presence of cancer cells
Basement membrane=
lamina, collagen
E-cadherin is a ____
transmembrane glycoprotein.
