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Merkel cell carcinoma expresses vasculogenic mimicry: demonstration in patients and experimental manipulation in xenografts.
Lezcano, Cecilia; Kleffel, Sonja; Lee, Nayoung; Larson, Allison R; Zhan, Qian; DoRosario, Andrew; Wang, Linda C; Schatton, Tobias; Murphy, George F.
Afiliación
  • Lezcano C; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Kleffel S; 1] Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
  • Lee N; 1] Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
  • Larson AR; 1] Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
  • Zhan Q; 1] Harvard Medical School, Boston, MA, USA [2] Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • DoRosario A; 1] Harvard Medical School, Boston, MA, USA [2] Center for Cutaneous Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
  • Wang LC; Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, USA.
  • Schatton T; 1] Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA [3] Transplantation Research Center, Children's Hospital, Boston, MA, USA.
  • Murphy GF; 1] Harvard Medical School, Boston, MA, USA [2] Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Lab Invest ; 94(10): 1092-102, 2014 Oct.
Article en En | MEDLINE | ID: mdl-25111691
Merkel cell carcinoma (MCC) is a highly virulent cutaneous neoplasm that, like melanoma, is a frequent cause of patient morbidity and mortality. The cellular mechanisms responsible for the aggressive behavior of MCC remain unknown. Vasculogenic mimicry (VM) is a phenomenon associated with cancer virulence, including in melanoma, whereby anastomosing laminin networks form in association with tumor cells that express certain endothelial genes. To determine whether VM is a factor in MCC, we employed a relevant xenograft model using two independent human MCC lines. Experimentally induced tumors were remarkably similar histologically to patient MCC, and both contained laminin networks associated with vascular endothelial-cadherin (CD144) and vascular endothelial growth factor receptor 1, as well as Nodal expression typical of VM in melanoma. Moreover, two established chemotherapeutic agents utilized for human MCC, etoposide and carboplatin, induced necrosis in xenografts on systemic administration while enriching for laminin networks in apparently resistant viable tumor regions that persisted. These findings for the first time establish VM-like laminin networks as a biomarker in MCC, demonstrate the experimental utility of the MCC xenograft model, and suggest that VM-rich regions of MCC may be refractory to conventional chemotherapeutic agents.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Neoplasias Cutáneas / Carcinoma de Células de Merkel / Ganglios Linfáticos / Neovascularización Patológica Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Aged80 / Animals / Humans / Middle aged Idioma: En Revista: Lab Invest Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Neoplasias Cutáneas / Carcinoma de Células de Merkel / Ganglios Linfáticos / Neovascularización Patológica Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Aged80 / Animals / Humans / Middle aged Idioma: En Revista: Lab Invest Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos