A44A1860d01 - Invasion and Metastasis Molecular Oncology...

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Unformatted text preview: Invasion and Metastasis Molecular Oncology Invasion and Metastasis Whole body scan: Fusion of a CT (computed X-ray tomography) scan & and a PET (positron-emission tomography ) Metastatic non-Hodgkin’s lymphoma Intervention period for carcinogenesis Progression of cancer from dysplasia to metastatic dissemination may extend as far as 10 years Progression of cancer from dysplasia to metastatic dissemination may extend as far as 10 years Pathogenesis of invasion and metastasis (I) • Metastasis can be described as secondary tumour formation via: – Haematogenous (bloodborne) dissemination – Lymphatic spread (e.g. lymph node metastasis) – Spread across body cavities (e.g. ovarian cancer: dissemination within the abdomen. Migration between BM & endothelium or along neurons) Pathogenesis of invasion and metastasis (II) Sequential steps in the pathogenesis of cancer Sequential steps in the pathogenesis of cancer metastasis metastasis How and when is metastatic potential determined? How and when is metastatic potential determined? Pre-metastatic niche Cancer is a multi-step process • Cancer is a multi-step process during which a cell acquires multiple genetic mutations. – Genes involved in growth control – gatekeepers – Genes regulating genomic stability – caretakers – Genes that affect non target genes – landscapers Landscapers = microenvironmental ‘effector’ Invasion • Invasive growth is a natural physiological process: – Formation and patterning of the embryo is a good model of invasive growth under physiological conditions. Embryonic cells must coordinate proliferation with other processes, such as migration, survival, matrix degradation and induction of cell polarity. – Axon guidance – Invasive contextual activity by epithelial cells during wound healing , when cells at the wound edge start dividing and moving over the provisional matrix to reconstitute tissue integrity Friedl et al., 2003, Nat. Rev. Cancer Plasticity of Plasticity of tumour tumour invasion mechanisms invasion mechanisms Patterns of invasion Patterns of invasion Cervical squamous cell carcinoma Melanoma cells Lobular breast carcinoma Mixed nodular and infiltrative basal cell carcinoma Invasion • Is the active translocation of neoplastic cells across tissue boundaries and through host cellular and extracellular barriers • A triad of necessary functions mediate invasion – Cellular adhesion – Local proteolysis – Motility Tumor microenvironment Tumor microenvironment • The microenvironment is defined as: 1. Insoluble extracellular matrix (ECM) The ECM contains collagens, laminins, fibronectin, vitronectin, tenascin and proteoglycans 2. Stroma consisting out of fibroblasts, adipose, vasculature and resident immune cells 3. The conventional milieu of cytokines and growth factors Microecology Microecology of the tumor of the tumor-- host invasion field host invasion field Epithelial cells and the microenvironment Epithelial cells and the microenvironment...
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A44A1860d01 - Invasion and Metastasis Molecular Oncology...

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