Neutrophil chemokines secreted by tumor cells mount a lung antimetastatic response during renal cell carcinoma progression
| Autor: | R. S. K. Chaganti, Venkata Thodima, Shai Posner, Ana M. Molina, Robert J. Motzer, Miguel A. López-Lago |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Cancer Research Chemokine Lung Neoplasms Stromal cell Neutrophils Fluorescent Antibody Technique Apoptosis Real-Time Polymerase Chain Reaction Article Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Genetics medicine Animals Humans Cytotoxic T cell RNA Messenger Interleukin 8 Carcinoma Renal Cell Molecular Biology Cell Proliferation 030304 developmental biology Mice Inbred BALB C 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction Cell growth Gene Expression Profiling medicine.disease Molecular biology Kidney Neoplasms 3. Good health Gene Expression Regulation Neoplastic CXCL5 030220 oncology & carcinogenesis Cancer cell Disease Progression Cancer research biology.protein Chemokines |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | The mechanism by which renal cell carcinoma (RCC) colonizes the lung microenvironment during metastasis remains largely unknown. To investigate this process, we grafted human RCC cells with varying lung metastatic potential in mice. Gene expression profiling of the mouse lung stromal compartment revealed a signature enriched for neutrophil-specific functions that was induced preferentially by poorly metastatic cells. Analysis of the gene expression signatures of tumor cell lines showed an inverse correlation between metastatic activity and the levels of a number of chemokines, including CXCL5 and IL8. Enforced depletion of CXCL5 and IL8 in these cell lines enabled us to establish a functional link between lung neutrophil infiltration, secretion of chemokines by cancer cells and metastatic activity. We further show that human neutrophils display a higher cytotoxic activity against poorly metastatic cells compared with highly metastatic cells. Together, these results support a model in which neutrophils recruited to the lung by tumor-secreted chemokines build an antimetastatic barrier with loss of neutrophil chemokines in tumor cells acting as a critical rate-limiting step during lung metastatic seeding. |
| Databáze: | OpenAIRE |
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