Mesenchymal Stromal Cells: Emerging Roles in Bone Metastasis

Abstract

Bone metastasis is the most advanced stage of many cancers and indicates a poor prognosis for patients due to resistance to anti-tumor therapies. The establishment of metastasis within the bone is a multistep process. To ensure survival within the bone marrow, tumor cells must initially colonize a niche in which they can enter dormancy. Subsequently, reactivation permits the proliferation and growth of the tumor cells, giving rise to a macro-metastasis displayed clinically as a bone metastatic lesion. Here, we review the evidences that suggest mesenchymal stromal cells play an important role in each of these steps throughout the development of bone metastasis. Similarities between the molecular mechanisms implicated in these processes and those involved in the homeostasis of the bone indicate that the metastatic cells may exploit the homeostatic processes to their own advantage. Identifying the molecular interactions between the mesenchymal stromal cells and tumor cells that promote tumor development may offer insight into potential therapeutic targets that could be utilized to treat bone metastasis.

Detection of Metastasis in a Patient-derived Orthotopic Xenograft (PDOX) Model of Undifferentiated Pleomorphic Sarcoma with Red Fluorescent Protein

“…We subsequently reported that stromal cells from the primary tumor traveled to the metastasis site in a PDOX model of pancreatic cancer (20). Recently, our results that stromal cells are essential for cancer cell homing and colonization to other organs have been confirmed (28)(29)(30).…”

“…All animal studies were conducted with an AntiCancer Institutional Animal Care and Use Committee (IACUC) protocol specifically approved for this study and in accordance with the principles and procedures outlined in the National Institute of Health Guide for the Care and Use of Animals under Assurance Number A3873-1. Mouse housing, feeding, surgical processes and imaging were conducted as previously described (23)(24)(25)(26)(27)(28)(29). The mice were humanely sacrificed as previously described (22)(23)(24)(25)(26).…”

Autophagy induces G0/G1 arrest and apoptosis in menstrual blood-derived endometrial stem cells via GSK3-β/β-catenin pathway

“…During the past decade, strong evidence has been demonstrated MSCs-based therapy is a rapidly developing field for diseases due to their multiple modes of action that collectively respond to many of the fundamental pathologic events [ 22 , 23 ]. MSCs were originally identified in the bone marrow and later detected in many other tissues.…”

The Endosteal Niche in Breast Cancer Bone Metastasis

“…All of these factors are well-known to affect several hallmarks of cancer (60,61). Whereas, the contribution of CAFs to primary tumor growth is intensely investigated and defined, the origin and role of CAFs in the metastatic environment, especially in breast cancer bone metastasis, remain poorly defined (62). Within the next chapters we discuss evidence that supports a role of CAFs during the progression and establishment of breast cancer bone metastasis.…”

Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling

“…Interactions between tumor cells and the host cells of the surrounding tumor microenvironment play an important role in tumor development, including cancer initiation, progression, and invasiveness [1]. The mesenchymal stem cells (MSCs) and macrophages are a particularly important component of the tumor microenvironment [2,3]. It has been suggested that MSCs promote tumor development and metastasis through several processes including the release of growth factors, enhancement of invasiveness and metastasis via the production of matrix metalloproteinases, and enabling immune evasion by providing an immunosuppressive environment [4][5][6].…”