Chemokine-Enhanced Chemotaxis of Lymphangioleiomyomatosis Cells with Mutations in the Tumor Suppressor TSC2 Gene

摘要: Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused LAM cells (smooth-muscle-like cells) that have mutations in the tumor suppressor genes tuberous sclerosis complex (TSC) 1 or 2 and capacity to metastasize. Since chemokines their receptors function chemotaxis of metastatic cells, we hypothesized may be recruited chemokine(s) lung. Quantification 25 bronchoalveolar lavage fluid from patients healthy volunteers revealed concentrations CCL2, CXCL1, CXCL5 were significantly higher samples than those volunteers. In vitro, CCL2 MCP-1 induced selective migration showing loss heterozygosity TSC2 a heterogeneous population grown explanted lungs. Additionally, frequencies single-nucleotide polymorphisms gene promoter region differed (p = 0.018), one polymorphism was associated more frequently with decline function. The presence (i.e., potential functionality) chemokine evaluated using immunohistochemistry sections 30 patients. Expression these varied among seen some cancers (e.g., breast cancer melanoma cells). These observations are consistent notion such as serve determine mobility specify site metastasis cell.