Michele Moschetta1, Yawara Kawano2, Antonio Sacco3,4, Angelo Belotti5, Rossella Ribolla5, Marco Chiarini4,6, Viviana Giustini4,7, Diego Bertoli4,7, Alessandra Sottini4,6, Monica Valotti4,6, Claudia Ghidini4,6, Federico Serana4,6, Michele Malagola8, Luisa Imberti4,6, Domenico Russo4,8, Alessandro Montanelli4,6, Giuseppe Rossi4,5, Michaela R Reagan9, Patricia Maiso10, Bruno Paiva10, Irene M Ghobrial11, Aldo M Roccaro12,13. 1. Sarah Cannon Research Institute UK, London, UK. 2. Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan. 3. Clinical Research Development and Phase I Unit, ASST Spedali Civili di Brescia, P.le Spedali Civili, n.1, 25123, Brescia, Italy. 4. CREA Laboratory, ASST Spedali Civili di Brescia, Brescia, Italy. 5. Department of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy. 6. Clinical Chemistry Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy. 7. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 8. Adult Bone Marrow Transplantation Unit, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy. 9. Maine Medical Center Research Institute, University of Maine, Scarborough, ME, USA. 10. Clinical and Translational Medicine, Clínica Universidad de Navarra, Pamplona, Spain. 11. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 12. Clinical Research Development and Phase I Unit, ASST Spedali Civili di Brescia, P.le Spedali Civili, n.1, 25123, Brescia, Italy. aldomaria.roccaro@asst-spedalicivili.brescia.it. 13. CREA Laboratory, ASST Spedali Civili di Brescia, Brescia, Italy. aldomaria.roccaro@asst-spedalicivili.brescia.it.
Abstract
PURPOSE OF THE REVIEW: Herein we dissect mechanisms behind the dissemination of cancer cells from primary tumor site to the bone marrow, which are necessary for metastasis development, with a specific focus on multiple myeloma. RECENT FINDINGS: The ability of tumor cells to invade vessels and reach the systemic circulation is a fundamental process for metastasis development; however, the interaction between clonal cells and the surrounding microenvironment is equally important for supporting colonization, survival, and growth in the secondary sites of dissemination. The intrinsic propensity of tumor cells to recognize a favorable milieu where to establish secondary growth is the basis of the "seed and soil" theory. This theory assumes that certain tumor cells (the "seeds") have a specific affinity for the milieu of certain organs (the "soil"). Recent literature has highlighted the important contributions of the vascular niche to the hospitable "soil" within the bone marrow. In this review, we discuss the crucial role of stromal cells and endothelial cells in supporting primary growth, homing, and metastasis to the bone marrow, in the context of multiple myeloma, a plasma cell malignancy with the unique propensity to primarily grow and metastasize to the bone marrow.
PURPOSE OF THE REVIEW: Herein we dissect mechanisms behind the dissemination of cancer cells from primary tumor site to the bone marrow, which are necessary for metastasis development, with a specific focus on multiple myeloma. RECENT FINDINGS: The ability of tumor cells to invade vessels and reach the systemic circulation is a fundamental process for metastasis development; however, the interaction between clonal cells and the surrounding microenvironment is equally important for supporting colonization, survival, and growth in the secondary sites of dissemination. The intrinsic propensity of tumor cells to recognize a favorable milieu where to establish secondary growth is the basis of the "seed and soil" theory. This theory assumes that certain tumor cells (the "seeds") have a specific affinity for the milieu of certain organs (the "soil"). Recent literature has highlighted the important contributions of the vascular niche to the hospitable "soil" within the bone marrow. In this review, we discuss the crucial role of stromal cells and endothelial cells in supporting primary growth, homing, and metastasis to the bone marrow, in the context of multiple myeloma, a plasma cell malignancy with the unique propensity to primarily grow and metastasize to the bone marrow.
Entities:
Keywords:
Bone marrow stroma; Bone marrow vasculature; Cancer-induced bone disease; Multiple myeloma
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