RESUMO
Integrin α11ß1 is a stromal cell-specific receptor for fibrillar collagens and is overexpressed in carcinoma-associated fibroblasts (CAFs). We have investigated its direct role in cancer progression by generating severe combined immune deficient (SCID) mice deficient in integrin α11 (α11) expression. The growth of A549 lung adenocarcinoma cells and two patient-derived non-small cell lung carcinoma (NSCLC) xenografts in these α11 knockout (α11(-/-)) mice was significantly impeded, as compared with wild-type (α11(+/+)) SCID mice. Orthotopic implantation of a spontaneously metastatic NCI-H460SM cell line into the lungs of α11(-/-) and α11(+/+) mice showed significant reduction in the metastatic potential of these cells in the α11(-/-) mice. We identified that collagen cross-linking is associated with stromal α11 expression, and the loss of tumor stromal α11 expression was correlated with decreased collagen reorganization and stiffness. This study shows the role of integrin α11ß1, a receptor for fibrillar collagen in differentiation of fibroblasts into CAFs. Furthermore, our data support an important role for α11 signaling pathway in CAFs, promoting tumor growth and metastatic potential of NSCLC cells and being closely associated with collagen cross-linking and the organization and stiffness of fibrillar collagen matrices.
Assuntos
Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Fibroblastos/fisiologia , Integrina beta1/fisiologia , Integrinas/fisiologia , Neoplasias Pulmonares/patologia , Receptores de Colágeno/fisiologia , Células Estromais/fisiologia , Animais , Linhagem Celular Tumoral , Colágeno/metabolismo , Cruzamentos Genéticos , Elasticidade , Proteínas da Matriz Extracelular/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Cadeias alfa de Integrinas , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Camundongos SCID , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Proteínas Quinases/metabolismo , Transdução de SinaisRESUMO
Sentinel lymph node biopsy is a novel method for the surgical management of patients with cervical cancer. Sentinel nodes have a higher chance of harbouring metastases than non-sentinel nodes. Assessment of sentinel nodes provides an opportunity to stage patients intraoperatively and avoid complete pelvic lymph node dissection and hence its morbidities. The aim of this article is to review the diagnostic performance of sentinel node detection, to determine which technique (blue dye, Tc or both) has the highest detection rate and sensitivity, and also to illustrate different approaches of histological assessment of the sentinel lymph node biopsy.
