Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance.
Elevated aldehyde dehydrogenase 1 (ALDH1) has been proposed as one of the possible candidates for a stem cell maker that can be used for the isolation of cancer stem cells from cancers such as leukemia and breast cancer. In the current study, we found that subpopulations with elevated ALDH1 were present in the human sarcoma cell lines, MG63 (osteosarcoma) and HT1080 (fibrosarcoma), using Aldefluor assay. Both ALDH1 positive and negative cell populations were isolated from the MG63 cell line, by cell-sorting using FACSAria. Both subpopulations had a comparable ability to differentiate similarly to the parental MG63, under normal monolayer culture condition. Subpopulations with the ability to form spheres in anchorage-independent, serum-starved conditions showed increased ALDH1 mRNA expression in addition to strong mRNA expression of the stem cell-related genes, such as Nanog, Oct3/4, Stat3 and Sox2, and possessed ability for self-renewal with secondary sphere formation. Sarcosphere cells from the MG63 cell line showed strong chemo-resistance against both doxorubicin and cisplatin compared with monolayer, adherent cells. In conclusion, sphere-forming cells with elevated ALDH1 are a possible candidate for sarcoma stem cells, possessing strong chemo-resistant capacities. Although ALDH1 elevation was not sufficient for representing sarcoma stem cells, the efficient detoxification could contribute to the chemo-resistant properties of the stem-like sphere cells form human sarcoma.
Honoki
Kanya
K
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan. kahonoki@naramed-u.ac.jp
Fujii
Hiromasa
H
Kubo
Atsushi
A
Kido
Akira
A
Mori
Toshio
T
Tanaka
Yasuhito
Y
Tsujiuchi
Toshifumi
T
D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D050697:Retinal Dehydrogenase; D012509:Sarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007527:Isoenzymes; D004317:Doxorubicin; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D002945:Cisplatin