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The role of the uPAR in tumor progression

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The role of the uPAR in tumor progression

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Samenvatting

The urokinase receptor (uPAR) is well known for its role in cell migration, invasion and tumor progression. Using uPAR knock out (ko) mice, we tested the hypothesis that uPAR may participate in tumor development by regulating expansion of the stem cell compartment, migration of these same skin stem cells within the tissue and inhibition of differentiation. After skin activation by an injury or simply by shaving the mice, so inducing the anagen phase, uPAR ko epidermis showed a reduced capacity to heal the wounds and a reduced hyperproliferation of the hair germ which is moving downwards into the dermis, compared to the wild type mice. Emigration of the upper follicular stem cells (progeny population) into the epidermis is clearly decreased in uPAR ko skin, demonstrating that uPAR contributes for populations of follicular keratinocytes to epidermis regeneration during a time of tissue expansion, which could be after an injury or during early stages of tumor progression. Besides, other experiments demonstrated that uPAR deficiency, not only reduces keratinocytes proliferation and delays epidermis and hair follicle regeneration, but accelerates also the terminal differentiation. Involucrin is in fact up-regulated by uPAR ko mice both in anagen and telogen phase. The fact that during the anagen phase, Rac1 activation is increased and that Myc expression is down-regulated in uPAR wt mice compared to the ko, suggests the possible mechanism by which uPAR regulates activated epidermis regeneration. These findings offer an opportunity for gaining insight into the earliest stages of neoplastic development.

Toon meer
OrganisatieHogeschool Utrecht
OpleidingBiologie en Medisch Laboratorium Onderzoek
AfdelingLife Sciences en Chemistry
PartnersUniversità vita Salute – San Raffaele Milano
Jaar2007
TypeBachelor
TaalEngels

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