Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression

被引:481
作者
Comito, G. [1 ]
Giannoni, E. [1 ]
Segura, C. P. [1 ]
Barcellos-de-Souza, P. [1 ]
Raspollini, M. R. [2 ]
Baroni, G. [2 ]
Lanciotti, M. [3 ]
Serni, S. [3 ]
Chiarugi, P. [1 ,4 ]
机构
[1] Univ Florence, Dept Expt & Clin Biomed Sci, Viale Morgagni 50, I-50134 Florence, Italy
[2] Univ Florence, Histol & Mol Diagnost Univ, Careggi Hosp, I-50134 Florence, Italy
[3] Univ Florence, Careggi Hosp, Dept Urol, I-50134 Florence, Italy
[4] Ctr Res Transfer & High Educ DenoTHE, Florence, Italy
关键词
prostate carcinoma progression; cancer-associated fibroblasts; cancer-associated macrophages; M1/M2 macrophage polarization; IL-6; SDF-1; ENDOTHELIAL PROGENITOR CELLS; TUMOR PROGRESSION; OXIDATIVE STRESS; GROWTH; MICROENVIRONMENT; DIFFERENTIATION; ANGIOGENESIS; ACTIVATION; TRANSITION; MONOCYTES;
D O I
10.1038/onc.2013.191
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Inflammation is now acknowledged as an hallmark of cancer. Cancer-associated fibroblasts (CAFs) force a malignant cross talk with cancer cells, culminating in their epithelial-mesenchymal transition and achievement of stemness traits. Herein, we demonstrate that stromal tumor-associated cells cooperate to favor malignancy of prostate carcinoma (PCa). Indeed, prostate CAFs are active factors of monocyte recruitment toward tumor cells, mainly acting through stromal-derived growth factor-1 delivery and promote their trans-differentiation toward the M2 macrophage phenotype. The relationship between M2 macrophages and CAFs is reciprocal, as M2 macrophages are able to affect mesenchymal-mesenchymal transition of fibroblasts, leading to their enhanced reactivity. On the other side, PCa cells themselves participate in this cross talk through secretion of monocyte chemotactic protein-1, facilitating monocyte recruitment and again macrophage differentiation and M2 polarization. Finally, this complex interplay among cancer cells, CAFs and M2 macrophages, cooperates in increasing tumor cell motility, ultimately fostering cancer cells escaping from primary tumor and metastatic spread, as well as in activation of endothelial cells and their bone marrow-derived precursors to drive de novo angiogenesis. In keeping with our data obtained in vitro, the analysis of patients affected by prostate cancers at different clinical stages revealed a clear increase in the M2/M1 ratio in correlation with clinical values. These data, coupled with the role of CAFs in carcinoma malignancy to elicit expression of stem-like traits, should focus great interest for innovative strategies aimed at the co-targeting of inflammatory cells and fibroblasts to improve therapeutic efficacy.
引用
收藏
页码:2423 / 2431
页数:9
相关论文
共 45 条
[1]
The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages [J].
Allavena, Paola ;
Sica, Antonio ;
Solinas, Graziella ;
Porta, Chiara ;
Mantovani, Alberto .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2008, 66 (01) :1-9
[2]
Cancer-related inflammation: Common themes and therapeutic opportunities [J].
Balkwill, Frances R. ;
Mantovani, Alberto .
SEMINARS IN CANCER BIOLOGY, 2012, 22 (01) :33-40
[3]
Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species [J].
Cat, Bahar ;
Stuhlmann, Dominik ;
Steinbrenner, Holger ;
Alili, Lirija ;
Holtkoetter, Olaf ;
Sies, Helmut ;
Brenneisen, Peter .
JOURNAL OF CELL SCIENCE, 2006, 119 (13) :2727-2738
[4]
Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression [J].
Cirri, Paolo ;
Chiarugi, Paola .
CANCER AND METASTASIS REVIEWS, 2012, 31 (1-2) :195-208
[5]
Stromal fibroblasts synergize with hypoxic oxidative stress to enhance melanoma aggressiveness [J].
Comito, Giuseppina ;
Giannoni, Elisa ;
Di Gennaro, Paola ;
Segura, Coral Pons ;
Gerlini, Gianni ;
Chiarugi, Paola .
CANCER LETTERS, 2012, 324 (01) :31-41
[6]
Role of tissue stroma in cancer cell invasion [J].
De Wever, O ;
Mareel, M .
JOURNAL OF PATHOLOGY, 2003, 200 (04) :429-447
[7]
Malignant cells facilitate lung metastasis by bringing their own soil [J].
Duda, Dan G. ;
Duyverman, Annique M. M. J. ;
Kohno, Mitsutomo ;
Snuderl, Matija ;
Steller, Ernst J. A. ;
Fukumura, Dai ;
Jain, Rakesh K. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (50) :21677-21682
[8]
Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-κB-Dependent Manner [J].
Erez, Neta ;
Truitt, Morgan ;
Olson, Peter ;
Hanahan, Douglas .
CANCER CELL, 2010, 17 (02) :135-147
[9]
Reciprocal Metabolic Reprogramming through Lactate Shuttle Coordinately Influences Tumor-Stroma Interplay [J].
Fiaschi, Tania ;
Marini, Alberto ;
Giannoni, Elisa ;
Taddei, Maria Letizia ;
Gandellini, Paolo ;
De Donatis, Alina ;
Lanciotti, Michele ;
Serni, Sergio ;
Cirri, Paolo ;
Chiarugi, Paola .
CANCER RESEARCH, 2012, 72 (19) :5130-5140
[10]
Collective cell migration in morphogenesis and cancer [J].
Friedl, P ;
Hegerfeldt, Y ;
Tusch, M .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2004, 48 (5-6) :441-449