CELL INVASION AND METASTASIS

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cell migration

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Presented by Kamarapu mounika(MD04) Pulugu priyanka(MD08) department of Medical devices

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CELL INVASION : Cell invasion is related to cell migration , and defines the ability of cells to become motile and to navigate through the extracellular matrix within a tissue or to infiltrate neighbouring tissues.

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1) Translocation of cells across extracellular matrix barriers. 2) Lysis of matrix protein by specific proteinases. 3) Cell migration. 10

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Matrix degrading enzymes Cell adhesion Cell motility 11

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Most important cell-cell adhesion molecules. Reduce expression of E- cadherin and catenin increase the invasiveness of tumor cells 12

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The epithelial–mesenchymal transition ( EMT ) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. A developmental regulatory program, referred to as the ‘‘epithelial-mesenchymal transition’’ (EMT). cells that undergo EMT gain stem cell-like properties, thus giving rise to Cancer Stem Cells (CSCs).

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Cont…. EMT-inducing transcription of the most steps of the invasion-metastasis save the final step of colonization. EMT-inducing transcription observed in nonepithelial tumor types sarcomas and neuroectodermal tumor

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Cont….. activation of parts of the EMT program or alternative regulatory programs.. These are… Heterotypic Contributions of Stromal Cells to Invasion & Metastatisis Plasticity in the Growth Program Distinct Forms of Invasion May Underlie Different Cancer Types The Daunting Complexity of Metastatic Colonization

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Cont….. Heterotypic Contributions of Stromal Cells to Invasion & Metastatisis ↑ crosstalk between cancer cells & cells of neoplastic stroma involved in aquired capability for Invasion & metastatisis . For Ex- MSCs are present in tumor stroma . Found to secrete CCL5/RANTES - response to signals released by cancer cells. (stimulate invasive behavior. Macrophages at the tumor periphery can foster local invasion by supplying matrix-degrading enzymes such as metalloproteinases and cysteine cathepsin proteases.

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Cont…. Plasticity in the Invasive Growth Program The role of contextual signals in inducing an invasive growth capability (often via an EMT) implies the possibility of reversibility , Cancer cells that have disseminated from a 1◦ tumor to a more distant tissue site may no longer benefit from the activated stroma and invasion/EMT-inducing signals . T he primary tumor; in the absence of ongoing exposure to these signals, carcinoma cells may revert to a noninvasive state. Thus, carcinoma cells

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Cont…. Distinct Forms of Invasion May Underlie Different Cancer Type The EMT program regulates a particular invasiveness termed as ‘‘ mesenchymal . Modes of invasion have been identified in cancer cell Collective invasion: involves nodules of cancer cells advancing masse into adjacent tissues Squamous cell carcinomas: cancers are rarely metastatic. Cancer cells show plasticity, enabling them to slither through existing in the ECM rather than clearing a path for themselves . Occurs in both the mesenchymal and collective forms of invasion. whether cancer cells participating in the collective and amoeboid forms of invasion employ components of the EMT program.

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Cont….. The Daunting Complexity of Metastatic Colonization… Metastasis can be broken down into two major phases : physical dissemination of cancer cells from the primary tumor to distant tissues, and the adaptation of these cells to foreign tissue microenvironments that results in successful colonization. i.e., the growth of micrometastases into macroscopic tumors . The multiple steps of dissemination would be in the Colonization. Evidenced by presence in patients of myriad micrometastases that have successfully disseminated but never progress to macroscopic metastatic tumors .

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Cont.. In some cancers: the 1◦ tumor may release systemic suppressor factors that renders micro metastasas dormant In other , such breast cancer & melanoma, macroscopic metastases may erupt after primary tumor has been surgically removed or PC destroyed. primary tumor cells entering the circulation endowed with the ability to colonize certain distant tissue sites Alternatively, the ability to colonize specific tissues may only develop in response to the selective pressure on already disseminated cancer cells to adapt to growth in foreign tissue microenvironments.