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Background Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. Methods Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression. Results Transformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24 h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive correlation between stromal MCT4 and tumor MCT1 expression. Conclusions Our data demonstrated that PCa progression may benefit of MCT1 expression in tumor cells and of MCT4 in tumor-associated stromal cells. Therefore, MCTs may result promising therapeutic targets in different phases of neoplastic transformation according to a strategy aimed to contrast the energy metabolic adaptation of PCa cells to stressful environments.

Background Nowadays, the histological examination of prostate core needle biopsies is still regarded as the gold standard in the diagnosis of prostate cancer (PCa). We investigated if the tissue print of core needle biopsy (biopsy print) could be used as adjunctive molecular investigative procedures in conjunction with routine histological examination of biopsy to improve PCa diagnosis. Methods The direct contact of PCa core biopsy to nitrocellulose membrane resulted in the release of a cellular micropeel that was used for downstream analytical procedures. Results By zymogram print-phoresis we demonstrated that matrix metalloproteases MMP-2 and MMP-9 could be visualized in biopsy prints and that the gelatinolytic activity was positively correlated with immunohistochemistry analysis of the same markers in matched bioptic specimens. Moreover, we compared the ability to detect the PCa-associated hypermethylation of GSTP1 promoter in DNA extracted from biopsy prints with those of the corresponding core needle biopsies. Biopsy prints demonstrated the same specificity of biopsies in detecting PCa (50%) while the sensitivity and the positive predictive value were lower than biopsies (56% vs 78% and 63% vs 70%, respectively). Conclusions Biopsy print, combining a molecular point of view to the routinely hystopathological analysis of prostate biopsies, should be a useful tool to improve the diagnosis of PCa.