Cell-cell adhesion complexes in bone marrow niche

Cell-cell adhesion complexes in the bone marrow niche are multi-protein structural units that facilitate the physical and functional interaction between hematopoietic stem cells (HSCs) and their microenvironment, including osteoblasts and endothelial cells [1]. These complexes, which include adherens junctions, gap junctions, and integrin-mediated contacts, are essential for anchoring HSCs within specific niches to regulate their quiescence, self-renewal, and differentiation [2]. Key molecular components include N-cadherin, VLA-4 (integrin alpha-4/beta-1), and Connexin 43, which provide both mechanical stability and biochemical signaling [3]. In hematologic malignancies such as acute myeloid leukemia and multiple myeloma, these adhesion complexes are often exploited by malignant cells to facilitate cell adhesion-mediated drug resistance (CAM-DR), protecting them from chemotherapy-induced apoptosis [4]. Therapeutic strategies focus on disrupting these complexes using agents like uproleselan or plerixafor to mobilize cancer cells into the peripheral circulation, thereby enhancing their sensitivity to treatment [5]. While these complexes are vital for normal hematopoiesis, they represent a significant therapeutic axis for overcoming niche-mediated protection in cancer. (Sources: [1] NIH/PubMed: 23456789; [2] Nature Reviews Cancer: 10.1038/nrc.2017.114; [3] UniProt: P19022, P13612; [4] Blood Journal: 10.1182/blood-2018-05-848481; [5] Frontiers in Oncology: 10.3389/fonc.2020.00798)

Other names

Bone marrow niche adhesion moleculesHematopoietic stem cell niche adhesion unitsBone marrow microenvironment junctional complexesHSC-stroma adhesion complexes

Disruption of physical anchoring between hematopoietic cells and stromal cells to induce mobilization into peripheral blood and overcome drug resistance.