Aldehyde dehydrogenase-positive melanoma stem cells in tumorigenesis, drug resistance and anti-neoplastic immunotherapy.

Cancer stem cells (CSCs), a rare subset of cancer cells, are well known for their self-renewing capacity. CSCs play a critical role in therapeutic failure and are responsible for poor prognosis in leukemia and various solid tumors. However, it is still unclear how CSCs initiate carcinogenesis and evade the immune response. In humans, the melanoma initiating cells (MICs) are recognized as the CSCs in melanomas, and were verified to possess CSC potentials. The enzymatic system, aldehyde dehydrogenase (ALDH) is considered to be a specific marker for CSCs in several tumors. The expression of ALDH in MICs may be closely correlated with phenotypic heterogeneity, melanoma-genesis, metastasis, and drug resistance. The ALDH+ CSCs/MICs not only serve as an indicator for therapeutic efficacy, but have also become a target for the treat of melanoma. In this review, we initially introduce the multiple capacities of MICs in melanoma. Then, we summarize in vivo and in vitro studies that illustrate the relationship between ALDH and MICs. Furthermore, understanding of chemotherapy resistance in melanoma relies on ALDH+ MICs. Finally, we review studies that focus on melanoma immunotherapies, rendering ALDH a potential marker to evaluate the efficacy of anti-neoplastic therapies or an adjuvant anti-melanoma target.