A mechanistic insight into the anti-metastatic role of the prostate specific antigen
| Autor: | Ilaria T. Cavarretta, Nadia Finocchio, Irene Locatelli, Francesco Montorsi, Alberto Briganti, Simona Bolamperti, Edoardo Guazzoni, Francesco Pellegrino, Giovanni Lavorgna, Andrea Salonia, Arianna Coghi, Roberta Lucianò, Walter Cazzaniga, Isabella Villa, Massimo Alfano |
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| Přispěvatelé: | Pellegrino, F., Coghi, A., Lavorgna, G., Cazzaniga, W., Guazzoni, E., Locatelli, I., Villa, I., Bolamperti, S., Finocchio, N., Alfano, M., Luciano, R., Briganti, A., Montorsi, F., Salonia, A., Cavarretta, I. |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
KLK3 urologic and male genital diseases Metastasis Extracellular matrix Prostate cancer PSA Prostate medicine RC254-282 Original Research Tumor microenvironment business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cancer medicine.disease Collagen I Prostate-specific antigen medicine.anatomical_structure Oncology Cancer cell Cancer research business |
| Zdroj: | Translational Oncology Translational Oncology, Vol 14, Iss 11, Pp 101211-(2021) |
| ISSN: | 1936-5233 |
| Popis: | Highlights • Prostate specific antigen is the standard circulating biomarker for prostate cancer. • We provide novel evidence that collagen 1 is an additional substrate for PSA. • PSA hampers first steps of cancer invasion. • Tissue-related PSA content/activity is inversely correlated to tumor progression. • Tissue-related PSA levels improve prediction of prostate cancer specific mortality. Aim Since its discovery Prostate Specific Antigen (PSA), also referred to as kallikrein-3 (KLK3), has been used as standard circulating biomarker for prostate cancer (PCa). However, its specificity remains not adequate and its mechanism of action still elusive. Therefore, deciphering PSA role throughout PCa-pathobiology would be relevant in improving both cancer diagnosis and outcome prediction. We investigated the possible role played by PSA on/in the tumor microenvironment and over the first steps of cancer invasion. Methods Fresh PCa-specimens and cell lines were used for ex-vivo/in-vitro invasion assays and assessment of prostate tissue-PSA (tPSA), type 1 collagen (COL1A1) and ß1-integrin expression. Tissue Cancer Genome Atlas (TCGA) and Decipher® datasets were considered to estimate tPSA clinical relevance. Results A more precise, inverse, correspondence between tPSA and clinical/pathological parameters was found than for circulating PSA. KLK3 combined with Gleason grade and pathologic stage, better predicted cancer-related mortality. Consistently, we demonstrated that PSA inhibits prostate extracellular-matrix (ECM) invasion by PCa cells. As for the mechanism of action, we provided novel information that PSA is able to cleave COL1A1, a main component of the ECM. Finally, ß1-integrin, a crucial COL1A1 transducing-receptor involved in tumor adhesion/invasion, resulted to be downregulated in PCa specimens with higher levels of tPSA. Conclusions By interfering with type 1 collagen and its downstream targets, PSA may hamper adhesion and path of the cancer cells through ECM and their migration ability, thus explaining the inverse correlation highlighted between prostate tPSA levels and clinically significant disease. |
| Databáze: | OpenAIRE |
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