Lecture 15 ECM in cancer metastasis Nov 23, 2016

Lecture 15 ECM in cancer metastasis Nov 23, 2016 - Lec 15...

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1 Lec 15 Nov 23 ECM and ovarian cancer
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1. The stroma plays a critical role in cancer progression 2. Peritoneal Metastasis 1. Is inhibited by mesothelial cells (2 mechanisms- secrete hyaluronan, conceal collagen-I matrix) 2. Is enhanced by inflammation (mesothelial retraction) 3. MT1-MMP enables cells to invade a collagen I-rich matrix 4. 3D matrix invasion requires factors additional to MT1-MMP… actinomyosin contraction? 5. Contractile behaviour associates with 1.compact spheroid formation 2.invasion -probably by aligning collagen fibers for migration 6. Rigid matrices promote cancer progression
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Fig. 1. Schematic overview of extracellular matrices, their major components, and cell surface receptors. ECMs are classified in two major types, the interstitial and pericellular matrices. Basement membrane, a type of pericellular matrix, is found between epi... Advanced Drug Delivery Reviews, 2015, Available online 10 November 2015 Theocharis et al Extracellular matrix structure
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Fig. 4. Human degradome and schematic representation of major extracellular matrix proteases. The human degradome is represented by at least 569 proteases distributed intra- and extracellularly, as well as at the cell membrane and subdivided into five families metalloproteases, serine proteases, cysteine proteases, aspartic acid proteases, and threonine proteases. In the right panel, a schematic representation of the variable structural protease domains is depicted. All proteases are basically expressed consisting of a signal sequence, a propeptide, that is cleaved upon activation, and a catalytic domain. However, several other structural domains distinguish the proteases families between each other, apart from the chemical moiety that participates in the hydrolysis, characterizing their localization and unique interactions. Advanced Drug Delivery Reviews xxx (2015) xxx–xxx
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Peritoneal metastasis is distinct from haematological metastasis EMT 3. Intravasation into blood vessel 2. Stromal matrix invasion 1. Escape from primary tumour-BM 2. degrad n How do cancer cells invade through these matrix barriers ? 5. Growth of secondary tumour at metastatic site; (often in bone or lungs) 4. Extravasation Haematological (blood-borne) metastasis: a multistep, inefficient process:
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Local- within abdominal cavity Primary tumour from ovary or fallopian tube epithelia Peritoneal Metastasis
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Local- within abdominal cavity Primary tumours from ovary or fallopian tube epithelia Carried by peritoneal fluid to secondary sites Peritoneal Metastasis …Or from gastrointestinal cancers that have invaded through to the serosal (peritoneal) membrane: Haematologic metastasis Peritoneal metastasis
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Local- within abdominal cavity Primary tumours from ovary or fallopian tube epithelia Carried by peritoneal fluid to secondary sites Peritoneal Metastasis …Or from gastrointestinal cancers that have invaded through to the serosal (peritoneal) membrane: Haematologic metastasis Peritoneal metastasis …Or from surgical perforation (accidental)
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Tumour cells exfoliate Carried by peritoneal fluid to secondary sites Peritoneal Metastasis
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