ABCB5 has been suggested to regulate skin progenitor cell fusion and mediate chemotherapeutic drug resistance in stem-like tumor cell subpopulations in human malignant melanoma. It is commonly over-expressed on circulating melanoma tumour cells. Furthermore, the ABCB5+ melanoma- initiating cells were demonstrated to express FLT1 (VEGFR1) receptor tyrosine kinase which was functionally required for efficient xenograft tumor formation, as demonstrated by shRNA knockdown experiments.
More recently, the ABCB5 molecule has been shown to be functionally relevant to carcinogenesis, demonstrated in colorectal cancer where it was shown to act as a mediator of 5-FU patient chemoresistance, and had a further direct role in tumorigenesis shown by shRNA-mediated colorectal cancer cell-line ABCB5 knockdowns that impeded tumorigenesis in human-to-mouse xenografts. These data revealed multiple roles for ABCB5 in cancer progression and chemoresistance, making it an attractive target for combined therapy. ABCB5 was similarly demonstrated in melanoma to be functionally important to multi-drug chemotherapy resistance, and tumor growth, controlling a proinflammatory signaling circuit utilizing TLR4, IL-1β, IL8 and CXCR1 signaling involving reciprocal paracrine interactions between the melanoma stem cell and tumor bulk population (in a rheostat manner termed "cancer stem cell rheostasis" by the authors). ABCB5 was shown to maintain the slow-cycling melanoma stem cells using this cytokine signaling loop, which became more differentiated upon ABCB5 interference (eg WFDC1 melanocyte differentiation marker increased, cancer cells were faster growing in vitro, tumors were more pigmented), or CXCR1 blockade (slow-cycling ABCB5+ cells entered the cell-cycle).
In normal physiology ABCB5 was shown to be a functional marker for adult limbal stem cells of the cornea; ABCB5+ cells could regrow a human cornea on a mouse with limbal stem cell deficiency (LSCD - a blindness disease of the corneal limbus) while ABCB5- cells could not, indicating a therapeutic potential for treating some types of blindness. ABCB5 was further shown to be anti-apoptotic in these adult stem cells.
^Allikmets R, Gerrard B, Hutchinson A, Dean M (October 1996). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Hum. Mol. Genet.5 (10): 1649–55. doi:10.1093/hmg/5.10.1649. PMID8894702.
^Frank NY, Pendse SS, Lapchak PH, Margaryan A, Shlain D, Doeing C, Sayegh MH, Frank MH (November 2003). "Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter". J. Biol. Chem.278 (47): 47156–65. doi:10.1074/jbc.M308700200. PMID12960149.
^Chen KG, Szakács G, Annereau JP, Rouzaud F, Liang XJ, Valencia JC, Nagineni CN, Hooks JJ, Hearing VJ, Gottesman MM (April 2005). "Principal expression of two mRNA isoforms (ABCB5 alpha and ABCB5 beta ) of the ATP-binding cassette transporter gene ABCB5 in melanoma cells and melanocytes". Pigment Cell Res.18 (2): 102–12. doi:10.1111/j.1600-0749.2005.00214.x. PMID15760339.
^Frank NY, Margaryan A, Huang Y, Schatton T, Waaga-Gasser AM, Gasser M, Sayegh MH, Sadee W, Frank MH (May 2005). "ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma". Cancer Res.65 (10): 4320–33. doi:10.1158/0008-5472.CAN-04-3327. PMID15899824.
^Wilson BJ, Saab KR, Ma J, Schatton T, Putz P, Zhan Q, Murphy GF, Gasser M, Waaga-Gasser AM, Frank NY, Frank MH (Jun 2014 IN-PRESS). "ABCB5 maintains melanoma-initiating cells through a pro-inflammatory cytokine signaling circuit.". Cancer Res. doi:10.1158/0008-5472.CAN-14-0582. PMID24934811.Check date values in: |date= (help)
Chen KG, Szakacs G, Annereau JP, et al. (2005). "Principal expression of two mRNA isoforms (ABCB 5alpha and ABCB 5beta ) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes". Pigment Cell Res.18 (2): 102–12. doi:10.1111/j.1600-0749.2005.00214.x. PMID15760339.
Huang Y, Anderle P, Bussey KJ, et al. (2004). "Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance". Cancer Res.64 (12): 4294–301. doi:10.1158/0008-5472.CAN-03-3884. PMID15205344.
Malorni W, Lucia MB, Rainaldi G, et al. (1998). "Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV-infected patients". Haematologica83 (1): 13–20. PMID9542318.
Matalon ST, Drucker L, Fishman A, et al. (2008). "The Role of heat shock protein 27 in extravillous trophoblast differentiation". J. Cell. Biochem.103 (3): 719–29. doi:10.1002/jcb.21476. PMID17661346.
Begley GS, Horvath AR, Taylor JC, Higgins CF (2005). "Cytoplasmic domains of the transporter associated with antigen processing and P-glycoprotein interact with subunits of the proteasome". Mol. Immunol.42 (1): 137–41. doi:10.1016/j.molimm.2004.07.005. PMID15488952.
Sharma BK, Manglik V, Elias EG. (2010). "Immuno-expression of human melanoma stem cell markers in tissues at different stages of the disease". J Surg Res.163 (1): e11–5. doi:10.1016/j.jss.2010.03.043. PMID20638684.
Gazzaniga P, Cigna E, Panasiti V, Devirgiliis V, Bottoni U, Vincenzi B, Nicolazzo C, Petracca A, Gradilone A. (2010). "CD133 and ABCB5 as stem cell markers on sentinel lymph node from melanoma patients". Eur J Surg Oncol.36 (12): 1211–4. doi:10.1016/j.ejso.2010.05.001. PMID20573479.