Affiliations: [a] Department of Pediatrics, Weill College of Medicine at Cornell University, New York, NY, USA | [b] Department of Cell and Developmental Biology, Weill College of Medicine at Cornell University, New York, NY, USA | [c] Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA | [d] Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA | National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Correspondence:
[**]
Corresponding author: David Lyden, M.D., Ph.D. Children's Cancer and Blood Foundation Laboratories, Box 284, 515 East 51st Street, Weill Cornell Medical College, New York, NY 10021, USA. Tel.: +1 212 746 3941; Fax: +1 212 746 8423; E-mail: dcl2001@med.cornell.edu or porte@mskcc.org
Note: [*] These authors contributed equally to this work.
Abstract: The long prevailing model of metastasis recognizes the importance of both “seed” and “soil” for metastatic progression [1]. Much attention has focused on understanding the molecular and genetic factors that confer an intrinsic metastatic advantage to certain tumor cells. Meanwhile, changes occurring within distant tissues, creating a “soil” conducive for tumor invasion, have been largely neglected. Bone marrow-derived hematopoietic progenitor cells (HPCs) recently emerged as key players in initiating these early changes, creating a receptive microenvironment at designated sites for distant tumor growth and establishing the “Pre-Metastatic Niche” [2]. This insight into the earliest stages in the metastatic cascade revises our concept of the metastatic “microenvironment” to include physiological cells recruited from the bone marrow. Moreover, the concept of pre-metastatic tissues as ‘niches’ similar to physiological stem cell niches establishes a paradigm in which disseminated tumor cells may reside within a highly defined microcosm, both supportive and regulatory, and which may confer specific functions on indwelling cells. Understanding the cellular and molecular cross-talk between “seed” and “soil” may further our understanding of the factors that govern both site-specific patterning in metastasis and the phenomenon of tumor dormancy. This may lead to therapeutic strategies to detect and prevent metastasis at its earliest inception.
Keywords: VEGFR-1, bone marrow progenitors, bone marrow microenvironment, peripheral niches, metastasis initiation, stroma
DOI: 10.3233/BD-2007-26106
Journal: Breast Disease, vol. 26, no. 1, pp. 65-74, 2007
