Stroma-derived but not tumor ADAMTS1 is a main driver of tumor growth and metastasis
| Autor: | María del Carmen Plaza-Calonge, Rubén Fernández-Rodríguez, Francisco Javier Rodríguez-Baena, Carlos Peris-Torres, Juan Carlos Rodríguez-Manzaneque, Estefania Martino-Echarri |
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| Přispěvatelé: | [Fernandez-Rodriguez, Ruben] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, GENYO, Granada 18016, Spain, [Javier Rodriguez-Baena, Francisco] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, GENYO, Granada 18016, Spain, [Martino-Echarri, Estefania] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, GENYO, Granada 18016, Spain, [Peris-Torres, Carlos] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, GENYO, Granada 18016, Spain, [del Carmen Plaza-Calonge, Maria] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, GENYO, Granada 18016, Spain, [Carlos Rodriguez-Manzaneque, Juan] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, GENYO, Granada 18016, Spain, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III from Spain, FEDER, Consejeria de Economia, Innovacion y Ciencia-Junta de Andalucia |
| Rok vydání: | 2016 |
| Předmět: |
Uveal Neoplasms
0301 basic medicine Pathology vasculature Carcinogenesis Melanoma Experimental Expression medicine.disease_cause Gene Induction Metastasis Extracellular matrix Mice Neoplasm Metastasis Melanoma Inhibition Mice Knockout Metalloproteinase Neovascularization Pathologic Host Proteases extracellular protease Oncology Deficiency Thrombospondin-1 Research Paper medicine.medical_specialty Stromal cell extracellular matrix Activation Down-Regulation Biology 03 medical and health sciences Stroma ADAMTS1 Protein Cell Line Tumor medicine Animals Humans Cell Proliferation Thrombospondin hypoxia Macrophages tumor stroma medicine.disease Xenograft Model Antitumor Assays Mice Inbred C57BL HEK293 Cells 030104 developmental biology Cancer research Angiogenesis Gene Deletion |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Ruben Fernandez-Rodriguez 1 , Francisco Javier Rodriguez-Baena 1 , Estefania Martino-Echarri 1 , Carlos Peris-Torres 1 , Maria del Carmen Plaza-Calonge 1 , Juan Carlos Rodriguez-Manzaneque 1 1 GENYO, Centre for Genomics and Oncological Research, Pfizer/Universidad de Granada/Junta de Andalucia, Granada 18016, Spain Correspondence to: Juan Carlos Rodriguez-Manzaneque, email: juancarlos.rodriguez@genyo.es Keywords: extracellular protease, extracellular matrix, hypoxia, tumor stroma, vasculature Received: February 24, 2016 Accepted: April 10, 2016 Published: April 22, 2016 ABSTRACT The matrix metalloprotease ADAMTS1 ( A Disintegrin And Metalloprotease with ThromboSpondin repeats 1 ) has been involved in tumorigenesis although its contributions appeared ambiguous. To understand the multifaceted actions of this protease, it is still required a deeper knowledge of its implication in heterogeneous tumor-stroma interactions. Using a syngeneic B16F1 melanoma model in wild type and ADAMTS1 knockout mice we found distinct stroma versus tumor functions for this protease. Genetic deletion of ADAMTS1 in the host microenvironment resulted in a drastic decrease of tumor growth and metastasis. However, the downregulation of tumor ADAMTS1 did not uncover relevant effects. Reduced tumors in ADAMTS1 KO mice displayed a paradoxical increase in vascular density and vascular-related genes; a detailed characterization revealed an impaired vasculature, along with a minor infiltration of macrophages. In addition, ex-vivo assays supported a chief role for ADAMTS1 in vascular sprouting, and melanoma xenografts showed a relevant induction of its expression in stroma compartments. These findings provide the first genetic evidence that supports the pro-tumorigenic role of stromal ADAMTS1. |
| Databáze: | OpenAIRE |
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