The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here, we conducted microarray analysis on 2,254 human breast cancer specimens and found increased expression of CCL5 and its receptor CCR5, but not CCR3, in the basal and HER-2 genetic subtypes. The subpopulation of human breast cancer cell lines found to express CCR5 displayed a functional response to CCL5. In addition, oncogene transformation induced CCR5 expression, and the subpopulation of cells that expressed functional CCR5 also displayed increased invasiveness. The CCR5 antagonists maraviroc or vicriviroc, developed to block CCR5 HIV coreceptor function, reduced in vitro invasion of basal breast cancer cells without affecting cell proliferation or viability, and maraviroc decreased pulmonary metastasis in a preclinical mouse model of breast cancer. Taken together, our findings provide evidence for the key role of CCL5/CCR5 in the invasiveness of basal breast cancer cells and suggest that CCR5 antagonists may be used as an adjuvant therapy to reduce the risk of metastasis in patients with the basal breast cancer subtype. Cancer Res; 72(15); 3839-50. Ó2012 AACR.

Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44+/CD24−/low or ALDH+ phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics have identified NF-κB, c-Jun, p21CIP1, and Forkhead-like-protein Dach1 in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs.

These results show that 4-HC not only exhibit antimetastatic effect in vivo, but also effectively reduces tumor growth and improves survival, even when it produce toxic effects. Although the molecular mechanism of 4-HC actions needs to be further defined, our data suggest that 4-HC may lead to the development of agents that could be used as adjuvants in the therapy of melanoma.

El presente artículo se inicia con una presentación de la Técnica de Rejilla (TR), enmarcada en el contexto de la Teoría de los Constructos Personales (TCP). A continuación, se expone la aplicación de la TR al caso de Ana diagnosticada por trastorno depresivo mayor, bulimia nerviosa y trastorno de personalidad por evitación, además de presentar otros síntomas variados. Se eligió este caso por su complejidad clínica y por la manera en que se ven reflejados los síntomas de la paciente en su estructura cognitiva, puesta de maniñesto por la TR. A pesar de que Ana pidió ayuda por iniciativa propia, en las sesiones se muestra reticente a hablar de sí misma, por lo que la TR resultó ser un buen medio de aproximación a la visión del mundo de la cliente, y un instrumento útil para formular hipótesis clínicas.Palabras clave: Técnica de la Rejilla, trastorno depresivo mayor, bulimia, trastorno de personalidad por evitación. Repertoiy Grid Tecbnique as an assessment instrument for case formulationThis paper begins with a presentation of the Repertory Grid Technique (RGT) within the framework of Personal Construct Theory. It follows with the description of the administration of a grid to Ana, a client diagnosed with major depressive disorder, bulimia nervosa, and avoidant personality disorder, as well as of other symptoms. This case is selected to illustrate the use of the RGT because of both its clinical complexity and the way in which her cognitive structure(as depicted by the RGT) is reflected in the presenting symptoms. Despite the fact that Ana eagerly requested help, during the therapy sessions she seems to be reluctant to talk about herself. The RGT proved to be a useful way of approaching her world view, and also a powerful instrument for case formulation.