Identification of progenitor cancer stem cell in lentigo maligna melanoma

ABSTRACT:  The potential role of stem cells in neoplasia has aroused considerable interest over the past few years. A number of known biologic characteristics of melanomas support the theory that they may originate in a mutated stem cell. Melanocytic stem cell markers have been described recently. Moreover, the CD133 cells that show surface markers for CD34 are stem cells primitive. These stem cells are capable of differentiating into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. The identification of cancer stem/initiating cells with a crucial role in tumor formation may open up new pharmacologic perspectives. The purpose of this study is to detect the expression of CD133 and CD34, two putative markers of cancer stem cells in the lentigo maligna melanoma. Thirty cases of lentigo maligna melanoma were analyzed using indirect immunohistochemical staining. The vast majority of the samples analyzed showed the presence of rare cells, which were clearly positive for CD133 and CD34. Strong CD133 and CD34 staining was found in the outer root sheath of the mid‐lower hair follicles, intermixed with atypical melanocytes extending along layers of the hair follicles. A number of these staminal cells were adjacent and intermixed with melanoma cells. This study supports the stem cell origin of this tumor and suggests that the precursor of the melanoma in question is a stem‐like cell rather than the primitive melanoblast committed to be exclusively involved in melanocytic differentiation.

[1]  T. Golub,et al.  Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9 , 2006, Nature.

[2]  Robert M Hoffman,et al.  Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Rafii,et al.  AC133/CD133/Prominin-1. , 2005, The international journal of biochemistry & cell biology.

[4]  G. Dontu,et al.  Mammary stem cells, self-renewal pathways, and carcinogenesis , 2005, Breast Cancer Research.

[5]  James R. Goldenring,et al.  Gastric Cancer Originating from Bone Marrow-Derived Cells , 2004, Science.

[6]  R. Henkelman,et al.  Identification of human brain tumour initiating cells , 2004, Nature.

[7]  M. Daniotti,et al.  Genetic progression of metastatic melanoma. , 2004, Cancer letters.

[8]  G. Dontu,et al.  Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells , 2004, Breast Cancer Research.

[9]  N. Bresolin,et al.  Human skin‐derived stem cells migrate throughout forebrain and differentiate into astrocytes after injection into adult mouse brain , 2004, Journal of neuroscience research.

[10]  S. Sell,et al.  Stem cell origin of cancer and differentiation therapy. , 2004, Critical reviews in oncology/hematology.

[11]  D. Wilson,et al.  Subungual melanoma with osteocartilaginous differentiation , 2003, Skeletal Radiology.

[12]  M. Hendrix,et al.  Angiogenesis: Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma , 2003, Nature Reviews Cancer.

[13]  B. Gilchrest,et al.  Fate of melanocytes during development of the hair follicle pigmentary unit. , 2003, The journal of investigative dermatology. Symposium proceedings.

[14]  J. Reis-Filho,et al.  Primary cutaneous malignant melanoma with lipoblast-like cells. , 2003, Archives of pathology & laboratory medicine.

[15]  M. A. Huber,et al.  Fibroblast activation protein: differential expression and serine protease activity in reactive stromal fibroblasts of melanocytic skin tumors. , 2003, The Journal of investigative dermatology.

[16]  S. Nishikawa,et al.  Dominant role of the niche in melanocyte stem-cell fate determination , 2002, Nature.

[17]  I. Weissman,et al.  Stem cells, cancer, and cancer stem cells , 2001, Nature.

[18]  J. Vogel,et al.  Murine epidermal label-retaining cells isolated by flow cytometry do not express the stem cell markers CD34, Sca-1, or Flk-1. , 2001, The Journal of investigative dermatology.

[19]  M. Herlyn,et al.  Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication , 2001, Oncogene.

[20]  Yann Barrandon,et al.  Morphogenesis and Renewal of Hair Follicles from Adult Multipotent Stem Cells , 2001, Cell.

[21]  A. Albino,et al.  Divergent cellular differentiation pathways during the invasive stage of cutaneous malignant melanoma progression. , 1999, The American journal of pathology.

[22]  D. Elder,et al.  Adenoviral gene transfer of beta3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma. , 1998, The American journal of pathology.

[23]  J. Kearney,et al.  AC133, a novel marker for human hematopoietic stem and progenitor cells. , 1997, Blood.

[24]  M. Herlyn,et al.  Nerve growth and expression of receptors for nerve growth factor in tumors of melanocyte origin. , 1991, The Journal of investigative dermatology.

[25]  M. Herlyn,et al.  Development of invasive and growth factor-independent cell variants from primary human melanomas. , 1991, Cancer research.

[26]  W. Clark.  The costs for consultations in dermatopathology. , 1984, The American Journal of dermatopathology.

[27]  J. A. Burch,et al.  Melanoma, a tumor based on a mutant stem cell? , 2006, The Journal of investigative dermatology.

[28]  P. Beachy,et al.  Urological Survey UROLOGICAL ONCOLOGY: PROSTATE CANCER Hedgehog Signalling in Prostate Regeneration, Neoplasia and Metastasis , 2005 .

[29]  W. Huttner,et al.  Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer , 2004, Cell and Tissue Research.

[30]  P. Meltzer,et al.  The stem cell plasticity of aggressive melanoma tumor cells , 2004 .

[31]  H. Yu,et al.  Melanocyte destruction and repigmentation in vitiligo: a model for nerve cell damage and regrowth. , 2002, Journal of biomedical science.

[32]  S. Cramer.  The neoplastic development of malignant melanoma. A biological rationale. , 1984, The American Journal of dermatopathology.

[33]  S. Cramer.  The histogenesis of acquired melanocytic nevi. Based on a new concept of melanocytic differentiation. , 1984, The American Journal of dermatopathology.

[34]  Cramer Sf.  The neoplastic development of malignant melanoma. A biological rationale. , 1984 .