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Questions and Answers
What is a common cause of anaemia in neoplasms?
What is a possible consequence of a space-occupying lesion in the brain?
Which type of neoplasm tends to destroy surrounding tissue?
What is a possible endocrine effect of neoplasms?
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What is the main function of matrix metalloproteinases (MMPs) in tumour invasion?
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What is a possible neuromuscular effect of neoplasms?
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What is the characteristic of epithelial to mesenchymal transition (EMT) in cancer cells?
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Why do neoplasms kill people?
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Which of the following is NOT a component of tumour invasion?
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What is the role of basement membrane in tumour invasion?
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How do matrix metalloproteinases (MMPs) regulate their activity?
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What is the role of cell adhesion in tumour invasion?
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What is the characteristic of membrane-type matrix metalloproteinases (MT-MMPs)?
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What is the role of zinc ion in matrix metalloproteinases (MMPs)?
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What is the stoichiometry of binding TIMP to MMP?
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Which of the following MMPs is believed to be of special importance in cancer invasion?
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What is the function of integrins in cell-matrix adhesion?
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What is the result of reduced expression of E-cadherin and catenin in tumour cells?
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What is the term for the spread of cancer cells through the blood vessels to various organs?
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What is the term for the ability of cancer cells to survive in the bloodstream despite being anchorage-dependent?
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What is the term for the theory that cancer cells require a specific environment to grow and metastasize?
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What is the term for the formation of new blood vessels by a tumour?
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Study Notes
Cancer Development and Metastasis
- Cancer is a population of cells that have lost normal controls of growth and differentiation, proliferating without check.
- Metastasis is the process by which a tumor cell leaves the primary tumor, travels to a distant site via the circulatory system, and establishes a secondary tumor.
Steps of Metastasis
- Invasion and infiltration of surrounding normal host tissue with penetration of small lymphatic or vascular channels.
- Release of neoplastic cells into the circulation.
- Survival in the circulation.
- Arrest in the capillary beds of distant organs.
- Penetration of the lymphatic or blood vessel walls followed by growth of the disseminated tumor cells.
Stages of Metastasis
- Invasion: primary tumor cells enter circulation.
- Circulation: to the secondary site of tumor growth.
- Colonization: formation of secondary tumor.
Tumor Invasion
- Translocation of cells across extracellular matrix barriers.
- Lysis of matrix protein by specific proteinases.
- Cell migration.
Components of Invasion
- Matrix degrading enzymes.
- Cell adhesion.
- Cell motility.
Matrix Degrading Enzymes
- Required for controlled degradation of extracellular matrix components.
- Proteases involved in this process are classified into serine-, cysteine-, aspartyl-, and metalloproteinases.
- Examples: matrix metalloproteinases (MMPs), collagenase, gelatinase, and stromelysins.
Matrix Metalloproteinases (MMPs)
- 16 members, subdivided into 4 groups, based on structural characteristics and substrate specificities.
- Soluble and secreted groups; collagenase, gelatinase, and stromelysins.
- Membrane type (MT-MMP) group is anchored in the plasma membrane.
- Zinc ion in the active center of the protease is required for catalytic activities.
Regulation of MMP
- Controlled by increased expression on a transcriptional level.
- MMPs are calcium-dependent proteases, synthesized as inactive proenzymes and activated by cleavage of a propeptide.
- MMP activity is regulated by specific inhibitors, tissue inhibitors of MMP (TIMPs).
Cell Attachment
- Integrin: cell-matrix adhesion.
- E-cadherin/catenin adhesion complex: cell-cell adhesion.
Cell Migration
- Small Rho GTPase family.
- Motility promoting factors: hepatocyte growth factor/scattering factor, insulin-like growth factor II, and autotaxin.
Routes of Metastasis
- Lymphatics.
- Blood vessels.
- Coelomic spaces.
Lymphatics
- Spread to local and distant lymph nodes.
- Frequent route of spread of carcinomas.
- Can involve lymphatics of lung.
Vascular Spread
- Spread through capillaries and veins to various organs.
- Common sites are lung, liver, bone, and brain.
Metastatic Inefficiency
- A sequence of inefficient steps.
- Not all malignant cells metastasize.
Local Effects of Neoplasms
- Benign: compression, altered function, obstruction, ulceration, and space-occupying lesions.
- Malignant: destruction of surrounding tissue, obstruction, constriction, ulceration, and infiltration.
Systemic Effects of Neoplasms
- Haematological: anaemia, low white cell and platelet counts, and thrombosis.
- Endocrine: excessive secretion of hormones, ectopic hormone secretion.
- Neuromuscular: problems with balance, sensory/sensorimotor neuropathies, myopathy, and myasthenia.
Why Do Neoplasms Kill People?
- Local effect: e.g., brain, perforation, haemorrhage.
- Replacement of essential body organs: malignant.
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Description
Learn about the gradual changes in cell morphology and properties that lead to cancer development, including the 5 major steps of metastasis.
