The prognostic value of LAMP3 in breast cancer was investigated. METHODS: Expression levels of LAMP3 in breast cancer cell lines and patient tissues were determined by real-time polymerase chain reaction and in a tissue microarray by immunohistochemistry. lmmunofluorescent staining was used to evaluate the distribution of LAMP3 in tumor xenografts relative to pimonidazole. Kaplan-Meier analysis as

well as multivariate Cox regression survival analyses were performed. RESULTS: LAMP3 was variably expressed in breast cancer cell lines and induced in an oxygen Fosbretabulin concentration-dependent manner. LAMP3 protein expression colocalized with hypoxic areas in breast cancer xenografts. LAMP3 mRNA was higher in breast tumors from patients with node-positive (P = .019) and/or steroid hormone receptor-negative tumors (P < .001). Breast cancer patients with high LAMP3 mRNA levels had more locoregional recurrences (P = .032 log-rank). This was limited to patients treated with lumpectomy and radiotherapy as primary treatment (n = 53, P = .009). No association with metastasis-free ZD1839 in vivo survival was found. In multivariate Cox regression analysis, LAMP3 remained as a statistically independent prognostic factor for locoregional recurrence (hazard

ratio, 2.76; 95% confidence interval, 1.01-7.5; P = .048) after correction for menopausal status, histologic grade, tumor size, nodal status, therapy, and steroid hormone receptor status. LAMP3 protein in breast cancer tissue proved also to be of prognostic relevance. CONCLUSIONS: Evidence was provided for an association of LAMP3 with tumor cell hypoxia in breast cancer xenografts. In AZD7762 the current breast cancer cohorts, LAMP3 had independent prognostic value. Cancer 2011;117:3670-81. (C) 2011 American Cancer Society.”
“Metastasis is the major cause of death for cancer patients with solid tumours, due mainly to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of metastasis

is therefore essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies. Metastasis is an inefficient process, such that very few cells that leave a tumour successfully form macrometastases in distant sites. This suggests that only a small subset of cells can successfully navigate the metastatic cascade and eventually re-initiate tumour growth to form life-threatening metastases. Recently, there has been growing support for the cancer stem cell (CSC) hypothesis which stipulates that primary tumours are initiated and maintained by a small subpopulation of cancer cells that possess “stem-like” characteristics.