Manuel Scimeca1, Chiara Antonacci2, Nicola Toschi3, Elena Giannini2, Rita Bonfiglio2, Claudio Oreste Buonomo4, Chiara Adriana Pistolese4, Umberto Tarantino5, Elena Bonanno6. 1. Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; OrchideaLab S.r.l., Morlupo, Rome, Italy; IRCCS San Raffaele Pisana, Rome, Italy. 2. Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. 3. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; Martinos Center for Biomedical Imaging, Boston, MA; Harvard Medical School, Boston, MA. 4. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. 5. Department of Orthopedics and Traumatology, University of Rome Tor Vergata, Policlinico Tor Vergata Foundation, Rome, Italy. 6. Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; TMALab s.r.l., Spin-off of University of Rome Tor Vergata, Rome, Italy. Electronic address: elena.bonanno@uniroma2.it.
Abstract
BACKGROUND: The development of bone metastasis from breast cancer results from a functional interaction between tumor cells and osteoclasts or osteoblasts. The main aim of this study was therefore to test the hypothesis that the appearance of breast osteoblast-like cells (BOLCs) in primary mammary lesions is a precursor (and hence an early predictor) of the formation of breast cancer metastases to bone. PATIENTS AND METHODS: In this study, we collected 64 breast infiltrating carcinomas, 50 breast benignant lesions, and 10 biopsies of bone metastasis selected from patients with infiltrated carcinoma. Immunohistochemical, western blot, and ultrastructural analysis allowed us to investigate the presence of BOLCs in breast cancer lesions and metastatic sites. RESULTS: We established the presence of a high amount of breast cancer cells that underwent mesenchymal transformation in infiltrating carcinomas. In addition, our results demonstrated that the microenvironment of breast cancer is very similar to the microenvironment of bone. We noted a significantly higher expression of BMP-2/4 and PTX3 in breast-infiltrating carcinomas compared with benign lesions. Moreover, we also identified numerous BOLCs positive to RANKL and Vitamin D receptor. Thanks to ultrastructural analysis, we also revealed the presence of BOLCs at the metastatic site. CONCLUSIONS: The identification of breast cancer cells with high affinity for a bone environment opens new perspectives on prevention and therapy of bone metastases from breast.
BACKGROUND: The development of bone metastasis from breast cancer results from a functional interaction between tumor cells and osteoclasts or osteoblasts. The main aim of this study was therefore to test the hypothesis that the appearance of breast osteoblast-like cells (BOLCs) in primary mammary lesions is a precursor (and hence an early predictor) of the formation of breast cancer metastases to bone. PATIENTS AND METHODS: In this study, we collected 64 breast infiltrating carcinomas, 50 breast benignant lesions, and 10 biopsies of bone metastasis selected from patients with infiltrated carcinoma. Immunohistochemical, western blot, and ultrastructural analysis allowed us to investigate the presence of BOLCs in breast cancer lesions and metastatic sites. RESULTS: We established the presence of a high amount of breast cancer cells that underwent mesenchymal transformation in infiltrating carcinomas. In addition, our results demonstrated that the microenvironment of breast cancer is very similar to the microenvironment of bone. We noted a significantly higher expression of BMP-2/4 and PTX3 in breast-infiltrating carcinomas compared with benign lesions. Moreover, we also identified numerous BOLCs positive to RANKL and Vitamin D receptor. Thanks to ultrastructural analysis, we also revealed the presence of BOLCs at the metastatic site. CONCLUSIONS: The identification of breast cancer cells with high affinity for a bone environment opens new perspectives on prevention and therapy of bone metastases from breast.
Authors: Frank He; Nora L Springer; Matthew A Whitman; Siddharth P Pathi; Yeonkyung Lee; Sunish Mohanan; Stephen Marcott; Aaron E Chiou; Bryant S Blank; Neil Iyengar; Patrick G Morris; Maxine Jochelson; Clifford A Hudis; Pragya Shah; Jennie A M R Kunitake; Lara A Estroff; Jan Lammerding; Claudia Fischbach Journal: Biomaterials Date: 2019-09-11 Impact factor: 12.479
Authors: Manuel Scimeca; Nicoletta Urbano; Rita Bonfiglio; Sarah Natalia Mapelli; Carlo Vittorio Catapano; Giuseppina Maria Carbone; Sara Ciuffa; Mario Tavolozza; Orazio Schillaci; Alessandro Mauriello; Elena Bonanno Journal: Contrast Media Mol Imaging Date: 2018-12-09 Impact factor: 3.161