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Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker.

Salazar-Onfray F, López M, Lundqvist A, Aguirre A, Escobar A, Serrano A, Korenblit C, Petersson M, Chhajlani V, Larsson O, Kiessling R - Br. J. Cancer (2002)

Bottom Line: Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes.Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas.Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro.

View Article: PubMed Central - PubMed

Affiliation: Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. fsalazar@machi.med.unchile.cl

ABSTRACT
The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT-PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a 'therapeutic window' to be exploited in cancer immunotherapy.

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Immunohistochemical detection of MC1R on primary melanoma tissues, normal keratinocytes and metastatic melanoma tissues. Paraffin sections of primary melanoma tissues and normal skin tissues and metastatic melanoma tissues were stained with mAb MP1-1B7 or IgG control followed by a biotinylated anti-Ig mAb and developed as described in Materials and Methods. (A) normal naevus 10× (left) and primary melanoma (right) (B) Comparison of the intensity of labelling between a primary melanoma (M) and keratinocytes (K)×10. (C) Melanoma infiltrated lymph node (MP1-1B7)×10. (D) Maxilar metastasis (MP1-1B7)×10. (E) Intestinal metastatic melanoma (MP1-1B7)×10, and (F) Intestinal metastatic melanoma (Ig negative control)×10. In panels A, E, and F, nuclear staining was performed using haematoxylin solution.
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fig2: Immunohistochemical detection of MC1R on primary melanoma tissues, normal keratinocytes and metastatic melanoma tissues. Paraffin sections of primary melanoma tissues and normal skin tissues and metastatic melanoma tissues were stained with mAb MP1-1B7 or IgG control followed by a biotinylated anti-Ig mAb and developed as described in Materials and Methods. (A) normal naevus 10× (left) and primary melanoma (right) (B) Comparison of the intensity of labelling between a primary melanoma (M) and keratinocytes (K)×10. (C) Melanoma infiltrated lymph node (MP1-1B7)×10. (D) Maxilar metastasis (MP1-1B7)×10. (E) Intestinal metastatic melanoma (MP1-1B7)×10, and (F) Intestinal metastatic melanoma (Ig negative control)×10. In panels A, E, and F, nuclear staining was performed using haematoxylin solution.

Mentions: Paraffin sections from melanomas or normal tissues were analysed by immunohistochemistry for MC1R expression. An intense specific staining was detected in all tested primary melanomas (n=15) (exemplified in Figure 2AFigure 2


Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker.

Salazar-Onfray F, López M, Lundqvist A, Aguirre A, Escobar A, Serrano A, Korenblit C, Petersson M, Chhajlani V, Larsson O, Kiessling R - Br. J. Cancer (2002)

Immunohistochemical detection of MC1R on primary melanoma tissues, normal keratinocytes and metastatic melanoma tissues. Paraffin sections of primary melanoma tissues and normal skin tissues and metastatic melanoma tissues were stained with mAb MP1-1B7 or IgG control followed by a biotinylated anti-Ig mAb and developed as described in Materials and Methods. (A) normal naevus 10× (left) and primary melanoma (right) (B) Comparison of the intensity of labelling between a primary melanoma (M) and keratinocytes (K)×10. (C) Melanoma infiltrated lymph node (MP1-1B7)×10. (D) Maxilar metastasis (MP1-1B7)×10. (E) Intestinal metastatic melanoma (MP1-1B7)×10, and (F) Intestinal metastatic melanoma (Ig negative control)×10. In panels A, E, and F, nuclear staining was performed using haematoxylin solution.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376124&req=5

fig2: Immunohistochemical detection of MC1R on primary melanoma tissues, normal keratinocytes and metastatic melanoma tissues. Paraffin sections of primary melanoma tissues and normal skin tissues and metastatic melanoma tissues were stained with mAb MP1-1B7 or IgG control followed by a biotinylated anti-Ig mAb and developed as described in Materials and Methods. (A) normal naevus 10× (left) and primary melanoma (right) (B) Comparison of the intensity of labelling between a primary melanoma (M) and keratinocytes (K)×10. (C) Melanoma infiltrated lymph node (MP1-1B7)×10. (D) Maxilar metastasis (MP1-1B7)×10. (E) Intestinal metastatic melanoma (MP1-1B7)×10, and (F) Intestinal metastatic melanoma (Ig negative control)×10. In panels A, E, and F, nuclear staining was performed using haematoxylin solution.
Mentions: Paraffin sections from melanomas or normal tissues were analysed by immunohistochemistry for MC1R expression. An intense specific staining was detected in all tested primary melanomas (n=15) (exemplified in Figure 2AFigure 2

Bottom Line: Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes.Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas.Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro.

View Article: PubMed Central - PubMed

Affiliation: Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. fsalazar@machi.med.unchile.cl

ABSTRACT
The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT-PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a 'therapeutic window' to be exploited in cancer immunotherapy.

Show MeSH
Related in: MedlinePlus