LOEX, Centre de recherche FRSQ du CHA de Québec, Quebec City, QC, Canada.
Clin Exp Metastasis. 2013 Jan;30(1):83-90. doi: 10.1007/s10585-012-9511-3. Epub 2012 Jul 13.
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 dermal-epidermal 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.
皮肤恶性黑色素瘤是一个重要的临床问题，因为它们具有高度侵袭性，可转移到远处部位，并且对现有治疗方法通常具有耐药性。导致黑色素瘤进展和化疗耐药的确切分子决定因素尚不清楚，部分原因是缺乏模拟人类黑色素瘤进展的相关实验模型。因此，我们开发了一种复杂的人类微血管化重建皮肤替代物，其中再现了天然皮肤的有组织的三维（3D）结构。将源自原发性和转移性部位的人类黑色素瘤细胞系添加到该 3D 模型中。我们的结果表明，应用于我们的皮肤替代模型中的黑色素瘤细胞的组织学特征和行为与其起源部位特异性相关。特别是，黑色素瘤细胞穿过表皮-真皮交界处的能力与其转移潜能相关。此外，还检测到一种产生 VEGF 的侵袭性转移性细胞系具有强烈的血管生成作用。该模型中存在微血管网络将允许研究转移过程的关键步骤。我们得出结论，这种体外人类肿瘤微血管化重建皮肤替代物有望成为一种多功能且有效的模型，可用于研究皮肤癌的进展，并筛选新的抗癌药物以改善当前的临床治疗方法。
