Skip to main content
. Author manuscript; available in PMC: 2018 Jul 11.
Published in final edited form as: Semin Oncol. 2017 Jul 11;44(2):101–112. doi: 10.1053/j.seminoncol.2017.06.005

Table 12.

Role of other CAMs in mediating chemoresistance

Cell type/CAM Consequences Reference/s
B-ALL/CD9

  • CD9 is overexpressed in B-ALL

  • It is a key mediator of ALL cell dissemination via C-X-C chemokine receptor type 4 (CXCR4)/Rac1 mediated migration and plays a significant role in homing and engraftment of B-ALL cells to the bone marrow and the testes

  • CD9+ cells had increased tumorigenic potential, self-renewal capacity, and drug resistance in B-ALL
Lung cancer, small cell/CD9

  • CD9 mediates chemoresistance by modulating avidity of integrin β1 leading to increased cell adhesion; whether CD9 behaves similarly in ALL remains to be determined
HSC/CD44

  • CD44 or homing cell adhesion receptor is involved in HSC adhesion
Lymphocytes/CD44

  • CD44 binds to endothelial cells and ECM components such as fibronectin to mediate lymphocyte recruitment to lymphoid organs
B-ALL and AML/CD44

  • CD44 expression is strongly augmented in ALL and is directly correlated with higher rates of relapse, suggesting its role in chemoresistance
Multiple myeloma/CD44

  • CD44 variant 9 splice isoform binds to stromal cells and is correlated with unfavorable prognosis
ALL/CXCR4

  • CXCR4 binds to stromal-derived factor 1 (SDF1) secreted by bone marrow stromal cells and induces calcium influx, integrin-mediated adhesion, chemotaxis and migration, and homing and engraftment in the bone marrow

  • CXCR4/SDF1 axis triggers multiple signaling cascades such as JAK/STAT, PI3K/Akt, Src, Ras/Raf/MEK/ERK providing defense against chemotherapy

  • CXCR4 is required for leukemia initiating activity and T-ALL cell migration

  • A small molecule competitive antagonist of CXCR4 – plerixafor acts as a chemosensitizing agent by mobilizing neoplastic cells from the bone marrow sanctuary
Multiple myeloma/ICAM1

  • ICAM1 binding to CD18 activated Src, ERK1/2 and c- myc pathways resulting in macrophage mediated drug resistance
HSC/Annexin II

  • Annexin II is a peripheral membrane protein expressed on stromal cells, osteoblasts and endothelial cells in bone marrow involved in HSC homing and engraftment
Multiple myeloma/Annexin II

  • Annexin II binding to annexin II receptor increases cell adhesion and promotes growth in the bone marrow
B-ALL/Annexin II

  • Annexin II interaction with p11 is required for ALL cell homing and engraftment and induces chemoresistance