Classical Protein Kinase C: a novel kinase target in breast cancer.

Classical protein kinase C (cPKC) enzymes are ser/thr protein kinases that have been an important factor in regulating a variety of cellular functions required for both in terms of health and disease. Therefore, precise control of cPKC-mediated signal is necessary for cellular homeostasis; however, their dysregulation leads to the development of several pathophysiological conditions including cancer. In cellular microenvironment, cPKC-mediated signaling is accompanied by multiple molecular mechanisms including phosphorylation, second messenger binding, and scaffold proteins. Functional cPKC interacts with a number of cellular proteins involved in the regulation of multiple biological functions such as cell growth, survival, migration, and adhesion. Further, the role of cPKC varies from cell to cell, substrate to substrate and, therefore, it is plausible to assume that the dysregulation of cPKC activity causes cellular transformation. Currently, there is no sufficient literature available to provide better understating to develop an effective therapeutic regimen to reverse pathophysiological condition caused by functionally dysregulated cPKC. Therefore, in the present review, we have focused on to provide a better and detail information on the various aspects of cPKC such as structure, mode of activation, regulation, and distinct cellular functions useful for the development of an effective therapeutic regimen against the breast cancer.

Suppressed expression of homotypic multinucleation, extracellular domains of CD172α (SIRP-α) and CD47 (IAP) receptors in TAMs upregulated by Hsp70-peptide complex in Dalton's lymphoma.

CD172α and CD47 are members of glycoprotein expressed on macrophages and various immune cells, promote immune recognition and T cell stimulation that priming phagocytosis of pathogens and apoptotic bodies and malignant cell. Tumour-releasing immunosuppressive factor promotes tumour growth and transforms the tumour resident M1 phenotype of macrophage to M2 phenotype (TAMs) that promotes tumour progression by downregulating the expression of different surface receptor including CD172α and CD47. Recent studies have reported that CD172α and CD47 are involved in the pathogenesis and promote malignancies such as lymphoma, leukaemia, melanoma, lung cancer and multiple myeloma, and their expression varies during infection and malignancies. Autologous Hsp70 is well recognized for its role in activating macrophages leading to enhance production of inflammatory cytokines. It has been observed that Hsp70 derived from normal tissues do not elicit tumour immunity, while Hsp70 preparation from tumour cell was able to elicit tumour immunity. However, the role of exogenous autologous hsp70 on the formation of giant cells is completely unknown. Therefore, in the present study, we sought to investigate the effect of Hsp70-peptide complex on the expression of CD172α and CD47 receptors in normal peritoneal macrophages (NMO) and TAMs. Finding shows that the expression of CD172α and CD47 enhances in TAMs and it reverts back the suppressed function of TAMs into M1 state of immunoregulatory phenotype that promotes tumour regression by enhanced multinucleation and phagocytosis of malignant cells and significantly enhances the homotypic fusion of macrophages and polykaryon formation in vitro by enhancing the expression of SIRPα and IAP.

Morphological effects of autologous hsp70 on peritoneal macrophages in a murine T cell lymphoma.

Heat shock protein 70 is highly conserved cytosolic protein which have important role in growth, development, and apoptosis. Hsp70 is well-known activator of macrophages and enhances the release of specific and non-specific effector molecules that have major role in tumor destruction and immunopotentiation of host. However, morphological effects of hsp 70 has not been carried out, therefore, morphological effects of hsp 70 on murine peritoneal macrophages were examined by light microscopy and scanning electron microscopy. Thioglycolate-induced peritoneal macrophages were prepared from BALB/c mice and cultured for 24 h in the presence of the hsp70. Tumor-associated macrophages treated with 10 µg/ml were varied in shape, mostly spindle shaped, i.e., stretched bidirectionally; surface ruffles were increased and their lamellipodia was prominent which suggest that hsp 70 treatment not only enhances the functional state of the peritoneal macrophages but also initiate immense morphological changes leading to increased endothelium adherence, increased antigen uptake, and increased migration to the inflammatory site.