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Title:
Development of a tridimensional microvascularized human skin substitute to study melanoma biology | Clinical & Experimental Metastasis
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Cutaneous malignant melanomas represent an important clinical problem because they are highly invasive, they can metastasize to distant sites and are typically resistant to available therapy. The precise molecular determinants responsible for melanoma progression and chemo-resistance are not yet known, in part due to lack of pertinent experimental models that mimic human melanoma progression. Accordingly, we developed a complex human microvascularized reconstructed skin substitute in which the organized three-dimensional (3D) architecture of the native skin is reproduced. Human melanoma cell lines derived from primary and metastatic sites were added to this 3D model. Our results demonstrate that histological features and behavior of melanoma cells applied in our skin substitute model are specific to their site of origin. In particular, the ability of melanoma cells to cross the dermalâepidermal junction correlates with their metastatic potential. In addition, a potent angiogenic effect was detected for an aggressive metastatic cell line that produces VEGF. The presence of a microvascular network within this model will allow studying a crucial step of the metastatic process. We conclude that such an in vitro human tumor microvascularized reconstructed skin substitute promises to be a versatile and efficient model to investigate skin cancer progression and to screen new anticancer drugs to improve currents clinical treatments.
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article, google, scholar, pubmed, melanoma, skin, cas, human, cell, model, cancer, metastasis, microvascularized, reconstructed, research, substitute, access, exp, privacy, cookies, content, auger, vitro, clin, publish, search, clinical, gibot, galbraith, huot, françois, cutaneous, threedimensional, metastatic, cells, tumor, matrix, data, information, log, journal, experimental, study, therapy, progression, models, primary, open, discover, dermatol,
Topics {âïž}
month download article/chapter pertinent experimental models hĂŽtel-dieu de quĂ©bec dermalâepidermal junction correlates centre de recherche reconstructed human skin animal-derived collagen matrix taking cell-matrix adhesions skin substitute model reconstructed skin model skin cellsâinvestigation modeling tissue-specific signaling cancer staging system related subjects full article pdf melanoma cells applied skin equivalent produced study melanoma biology american joint committee pre-clinical modeling privacy choices/manage cookies de gruijl fr important clinical problem human keratinocyte isolation 3d nanostructured environments cellâcell organization van kempen lc melanoma primary cultures tumor therapy article gibot cell surface markers tissue eng part cutaneous melanoma melanoma cells tumor metastasis european economic area potent angiogenic effect mechanical phenotypic plasticity lopez valle ca recombinant lentiviral vectors mihm mc jr skin equivalent conditions privacy policy check access drug resistance multidrug resistant variant dr dan lacroix instant access accepting optional cookies native skin
Questions {â}
- Herlyn M, Fukunaga-Kalabis M (2010) What is a good model for melanoma?
- Karpanen T, Alitalo K (2001) Lymphatic vessels as targets of tumor therapy?
- Mazzoleni G, Di Lorenzo D, Steimberg N (2009) Modelling tissues in 3D: the next future of pharmaco-toxicology and food research?
- Pepper MS (2001) Lymphangiogenesis and tumor metastasis: myth or reality?
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headline:Development of a tridimensional microvascularized human skin substitute to study melanoma biology
description:Cutaneous malignant melanomas represent an important clinical problem because they are highly invasive, they can metastasize to distant sites and are typically resistant to available therapy. The precise molecular determinants responsible for melanoma progression and chemo-resistance are not yet known, in part due to lack of pertinent experimental models that mimic human melanoma progression. Accordingly, we developed a complex human microvascularized reconstructed skin substitute in which the organized three-dimensional (3D) architecture of the native skin is reproduced. Human melanoma cell lines derived from primary and metastatic sites were added to this 3D model. Our results demonstrate that histological features and behavior of melanoma cells applied in our skin substitute model are specific to their site of origin. In particular, the ability of melanoma cells to cross the dermalâepidermal junction correlates with their metastatic potential. In addition, a potent angiogenic effect was detected for an aggressive metastatic cell line that produces VEGF. The presence of a microvascular network within this model will allow studying a crucial step of the metastatic process. We conclude that such an in vitro human tumor microvascularized reconstructed skin substitute promises to be a versatile and efficient model to investigate skin cancer progression and to screen new anticancer drugs to improve currents clinical treatments.
datePublished:2012-07-13T00:00:00Z
dateModified:2012-07-13T00:00:00Z
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Cancer Research
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Hematology
Surgical Oncology
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headline:Development of a tridimensional microvascularized human skin substitute to study melanoma biology
description:Cutaneous malignant melanomas represent an important clinical problem because they are highly invasive, they can metastasize to distant sites and are typically resistant to available therapy. The precise molecular determinants responsible for melanoma progression and chemo-resistance are not yet known, in part due to lack of pertinent experimental models that mimic human melanoma progression. Accordingly, we developed a complex human microvascularized reconstructed skin substitute in which the organized three-dimensional (3D) architecture of the native skin is reproduced. Human melanoma cell lines derived from primary and metastatic sites were added to this 3D model. Our results demonstrate that histological features and behavior of melanoma cells applied in our skin substitute model are specific to their site of origin. In particular, the ability of melanoma cells to cross the dermalâepidermal junction correlates with their metastatic potential. In addition, a potent angiogenic effect was detected for an aggressive metastatic cell line that produces VEGF. The presence of a microvascular network within this model will allow studying a crucial step of the metastatic process. We conclude that such an in vitro human tumor microvascularized reconstructed skin substitute promises to be a versatile and efficient model to investigate skin cancer progression and to screen new anticancer drugs to improve currents clinical treatments.
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Angiogenesis
Microvascularization
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Surgical Oncology
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