CD133 and ABCB5 as stem cell markers on sentinel lymph node from melanoma patients

Gazzaniga, Paola; Cigna, Emanuele; Panasiti, Vincenzo; Devirgiliis, Valeria; Bottoni, Ugo; Vincenzi, Bruno; Nicolazzo, Chiara; Petracca, Arianna; Gradilone, Angela

doi:10.1016/j.ejso.2010.05.001

Cited by 26 publications

(17 citation statements)

References 13 publications

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“…Moreover, our results revealed selective ABCB5 expression in PBMC of a subset of metastatic human melanoma patients but not in PBMC derived from healthy human controls as previously described [19], underlining the melanoma-specific expression pattern of this MMIC-associated gene. These findings resemble recent observations by others of melanoma-specific ABCB5 expression in a subset of patient sentinel lymph node biopsy specimens, but absent expression in all of a series of non-melanoma case-derived control lymphatic tissues [13]. …”

Section: Discussionsupporting

confidence: 90%

“…We and others have demonstrated that the chemoresistance mediator ABCB5 [14; 15] marks immunoevasive [16] subpopulations of MMIC that correlate with metastatic malignant melanoma progression in human patients [10; 12; 13] and experimental xenotransplantation models [22]. We therefore examined whether ABCB5 might also be expressed by melanoma CTC found capable of tumor initiation and metastasis formation in this study.…”

Section: Resultsmentioning

confidence: 99%

“…Our laboratory recently showed human malignant melanoma initiating cells (MMIC) to express the targetable biomarker [10; 12; 13; 14] and multidrug resistance mediator [14; 15], ATP-binding cassette subfamily B member 5 (ABCB5) [10]. In this study, proof of principle of immune-mediated MMIC destruction and consequent inhibition of tumor growth was demonstrated [10].…”

Section: Introductionmentioning

confidence: 98%

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Isolation of tumorigenic circulating melanoma cells

Lin

Alloo

et al. 2010

Biochemical and Biophysical Research Communications

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Circulating tumor cells (CTC) have been identified in several human malignancies, including malignant melanoma. However, whether melanoma CTC are tumorigenic and cause metastatic progression is currently unknown. Here we isolate for the first time viable tumorigenic melanoma CTC and demonstrate that this cell population is capable of metastasis formation in human-tomouse xenotransplantation experiments. The presence of CTC among peripheral blood mononuclear cells (PBMC) of murine recipients of subcutaneous (s.c.) human melanoma xenografts could be detected based on mRNA expression for human GAPDH and/or ATP-binding cassette subfamily B member 5 (ABCB5), a marker of malignant melanoma-initiating cells previously shown to be associated with metastatic disease progression in human patients. ABCB5 expression could also be detected in PBMC preparations from human stage IV melanoma patients but not healthy controls. The detection of melanoma CTC in human-to-mouse s.c. tumor xenotransplantation models correlated significantly with pulmonary metastasis formation. Moreover, prospectively isolated CTC from murine recipients of s.c. melanoma xenografts were capable of primary tumor initiation and caused metastasis formation upon xenotransplantation to secondary murine NOD-scid IL2Rγ null recipients. Our results provide initial evidence that melanoma CTC are tumorigenic and demonstrate that CTC are capable of causing metastatic tumor progression. These findings suggest a need for CTC eradication to inhibit metastatic progression and provide a rationale for assessment of therapeutic responses of this tumorigenic cell population to promising emerging melanoma treatment modalities.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Isolation of tumorigenic circulating melanoma cells

Lin

Alloo

et al. 2010

Biochemical and Biophysical Research Communications

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“…Several of the genes shown to play a role in the regulation of normal stem cell self-renewal (WNT, Sonic Hedgehog, Notch) have been found to be active in cancer in general. 23–37 Bmi-1, a gene involved in somatic stem cell self-renewal has been shown to be critical for cancer stem cell proliferation in hematologic malignancies. 26 Interestingly, it is also overexpressed in osteosarcoma but knockdown experiments do not reveal a functional role in its malignancy.…”

Section: Cancer Stem Cellsmentioning

confidence: 99%

Evidence for the osteosarcoma stem cell

Gibbs

Levings

Ghivizzani

2011

Current Orthopaedic Practice

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Osteosarcoma is a highly malignant bone tumor of children and young adults. Cytotoxic chemotherapy combined with aggressive surgery only has a 60% survival rate. Historically, chemotherapy has been developed assuming that all cells within a particular cancer are clonal and near identical. Appreciating the now apparent functional heterogeneity of osteosarcoma cells within and between individual tumors will likely be critical in developing much needed novel effective therapies. The foundation for this heterogeneity may lie in the so called “cancer stem cell” or tumorigenic cell of origin. In this brief review, we will examine the evidence for the existence of this cell and its potential importance for future therapies.

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“…Moreover, ABCB5 expression correlates with tumor virulence and clinical cancer progression in these malignancies (Cheung et al, 2011; Gazzaniga et al, 2010; Schatton et al, 2008; Sharma et al, 2010; Wilson et al, 2011). Given its role in MDR of multiple malignancies, we hypothesized that ABCB5 might also identify therapy-refractory tumor populations in MCC.…”

Section: Introductionmentioning

confidence: 99%

ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth

Kleffel

Lee

Lezcano

et al. 2016

Journal of Investigative Dermatology

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Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with profound but poorly understood resistance to chemotherapy, which poses a significant barrier to clinical MCC treatment. Here we show that ATP–binding cassette member B5 (ABCB5) confers resistance to standard-of-care MCC chemotherapeutic agents and provide proof-of-principle that ABCB5 blockade can inhibit human MCC tumor growth through sensitization to drug-induced cell cytotoxicity. ABCB5 expression was detected in both established MCC lines and clinical MCC specimens at levels significantly higher than those in normal skin. Carboplatin and etoposide-resistant MCC cell lines exhibited increased expression of ABCB5, along with enhanced ABCB1 and ABCC3 transcript expression. ABCB5-expressing MCC cells in heterogeneous cancers preferentially survived treatment with carboplatin and etoposide in vitro and in human MCC xenograft-bearing mice in vivo. Moreover, MCC patients also exhibited enhanced ABCB5 positivity following carboplatin- and etoposide-based chemotherapy, pointing to clinical significance of this chemoresistance mechanism. Importantly, ABCB5 blockade reversed MCC drug resistance and impaired tumor growth in xenotransplantation models in vivo. Our results establish ABCB5 as a chemoresistance mechanism in MCC and suggest utility of this molecular target for improved MCC therapy.

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CD133 and ABCB5 as stem cell markers on sentinel lymph node from melanoma patients

Cited by 26 publications

References 13 publications

Isolation of tumorigenic circulating melanoma cells

Isolation of tumorigenic circulating melanoma cells

Evidence for the osteosarcoma stem cell

ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth

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