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Questions and Answers
What is a common cause of anaemia in neoplasms?
What is a common cause of anaemia in neoplasms?
What is a possible consequence of a space-occupying lesion in the brain?
What is a possible consequence of a space-occupying lesion in the brain?
Which type of neoplasm tends to destroy surrounding tissue?
Which type of neoplasm tends to destroy surrounding tissue?
What is a possible endocrine effect of neoplasms?
What is a possible endocrine effect of neoplasms?
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What is the main function of matrix metalloproteinases (MMPs) in tumour invasion?
What is the main function of matrix metalloproteinases (MMPs) in tumour invasion?
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What is a possible neuromuscular effect of neoplasms?
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?
What is the characteristic of epithelial to mesenchymal transition (EMT) in cancer cells?
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Why do neoplasms kill people?
Why do neoplasms kill people?
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Which of the following is NOT a component of tumour invasion?
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?
What is the role of basement membrane in tumour invasion?
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How do matrix metalloproteinases (MMPs) regulate their activity?
How do matrix metalloproteinases (MMPs) regulate their activity?
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What is the role of cell adhesion in tumour invasion?
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)?
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)?
What is the role of zinc ion in matrix metalloproteinases (MMPs)?
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What is the stoichiometry of binding TIMP to MMP?
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?
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?
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?
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?
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?
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?
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?
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.
