Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness.
Although cancer-associated fibroblasts (CAF) are key determinants in the malignant progression of cancer, their functional contribution to this process is still unclear. Analysis of the mutual interplay between prostate carcinoma cells and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in fibroblast activation. In turn, activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous metastases. CAF-induced EMT leads prostate carcinoma cells to enhance expression of stem cell markers, as well as the ability to form prostaspheres and to self-renew. Hence, the paracrine interplay between CAFs and cancer cells leads to an EMT-driven gain of cancer stem cell properties associated with aggressiveness and metastatic spread.
Giannoni
Elisa
E
Department of Biochemical Sciences, University of Florence, Tuscany, Italy.
Bianchini
Francesca
F
Masieri
Lorenzo
L
Serni
Sergio
S
Torre
Eugenio
E
Calorini
Lido
L
Chiarugi
Paola
P
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010447:Peptide Hydrolases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology
D015850:Interleukin-6; D010447:Peptide Hydrolases; D020782:Matrix Metalloproteinases