The Role of Chemokines in Breast Cancer Pathology and Its Possible Use as Therapeutic Targets

Chemokines are small proteins that primarily regulate the traffic of leukocytes under homeostatic conditions and during specific immune responses. The chemokine-chemokine receptor system comprises almost 50 chemokines and approximately 20 chemokine receptors; thus, there is no unique ligand for each receptor and the binding of different chemokines to the same receptor might have disparate effects. Complicating the system further, these effects depend on the cellular milieu. In cancer, although chemokines are associated primarily with the generation of a protumoral microenvironment and organ-directed metastasis, they also mediate other phenomena related to disease progression, such as angiogenesis and even chemoresistance. Therefore, the chemokine system is becoming a target in cancer therapeutics. We review the emerging data and correlations between chemokines/chemokine receptors and breast cancer, their implications in cancer progression, and possible therapeutic strategies that exploit the chemokine system

Privatisation and quasi-markets

Paper presented at the EACES First Trento Workshop, University of Trento (IT), 1-2 Mar 1991Available from British Library Document Supply Centre- DSC:8490.3304(7) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Immunolocalization of F-actin (red) of control, T₄ and DHT treated parasites.

<p>Phase contrast of the control sections of the slides obtained by Tissue-Teck fixing are shown in upper panel from left to right, control (C), testosterone (T₄) and dihydrotestosterone (DHT). In lower panel, red tiny spots are produced by the specific binding of the anti-α-tubulin stained with rhodamine-coupled phalloidin to cytoskeletal F-actin. F-actin proteins inside the bladder wall and at the level of the tegument in the tissue of control parasites and those treated with T₄ and DHT. Scale bar corresponds to 10 μm.</p

Specific expression of actin, tubulin and myosin in <i>Taenia crassiceps</i> cysticerci by flow cytometry.

<p>Dot plot depicted in Fig 1 (A), represents size and complexity of the <i>T</i>. <i>crassiceps</i> cells used for staining and detection of cytoskeletal proteins. FACS analysis of parasitic actin (B and C), tubulin (D and E) and myosin (F and G). Histograms (B, D and F) show a representative experiment of actin, tubulin and myosin-detection. Pink line: Unstained cells cultured in the presence of vehicle; Purple line: Unspecific secondary staining from FITC- (Sec Ab); Green line: Actin (B), Tubulin (D) or Myosin (F) specific expression in unstimulated cells cultured in the presence of vehicle; Light blue: Actin (A), Tubulin (C) or Myosin (E) specific expression in T4-stimulated cells; and Orange line: Actin (A), Tubulin (C) or Myosin (E) specific expression in DHT-stimulated cells. Panels (C, E and G) show the relative expression in steroid-treated and control cells. Relative expression was calculated according to: MFI of actin, tubulin or myosin stained cells / MFI secondary antibody stained cells. Data show the mean ± SE of five independent experiments.</p

Immunolocalization of α-tubulin (green) of control, T₄ and DHT treated parasites.

<p>Phase contrast of the control sections of the slides obtained by Tissue-Teck fixing are shown in upper panel from left to right, control (C), testosterone (T₄) and dihydrotestosterone (DHT). In lower panel, green tiny spots are produced by the specific binding of the anti-α-tubulin stained with alexa-488 antibody to cytoskeletal α-tubulin. Tubulin protein inside the bladder wall and at the level of the tegument in the tissue of control parasites and those treated with T₄ and DHT. Scale bar corresponds to 10 μm.</p

Docking of testosterone or dihydrotestosterone to actin, tubulin and myosin.

<p>Dihydrotestosterone (green or red) and testosterone (cyan) docking to actin (A and D), myosin VIb (B and E) and tubulin (C and F). We show the higher affinity sites according to neural-network scoring.</p

Immunolocalization of nuclei after staining with DAPI of control, T₄- and DHT-treated cysticerci.

<p>Phase contrast of the control sections of the slides obtained by Tissue-Teck fixing are shown in upper panel from left to right, control (C), testosterone (T₄) and dihydrotestosterone (DHT). In lower panel, DAPI was used to detect nuclei in frozen tissue sections fixed with Tissue-Teck. Treatment with both steroids induced changes in the distribution of nuclei, which also affected the morphology of FCs. Cysticerci were observed under an SEM Zeiss DSM-950 after five days of treatment with 50 μg/ml of each steroid. Scale bar corresponds to 10 μm.</p

Confocal microscopy depicting flame cells of control, T₄ and DHT-treated parasites.

<p>Phase contrast of the control sections of the slides obtained by Tissue-Teck fixing are shown in upper panel from left to right, control (C), testosterone (T₄) and dihydrotestosterone (DHT). In lower panel, flame cells of control, cysticerci treated with T₄ and DHT are presented. The normal number and distribution of flame cells is observed in control, while in those parasites exposed to T₄ and those exposed to DHT there is a decreased and disrupted pattern of flame cells. Scale bar corresponds to 10 μm.</p