Currently Cancer is the leading cause of death worldwide. Malignancy or cancer is a class of diseases characterized by uncontrolled cell growth that eventually invade other tissues and develop secondary malignant growth at other sites by metastasis. Intercellular communication plays a major role in cancer, particularly in the process of cell proliferation and coordination which in turn leads to tumor invasion, metastasis and development of resistance to therapy. Cells communicate among themselves in a variety of ways, namely: i) via gap junctions with adjacent cells; ii) via exosomes with nearby cells; and iii) via chemical messengers with distant cells. Besides, cell - cell connection by tunneling nanotubes (TnTs) is recently gaining importance where intercellular components are transferred between cells. In general cell organelles like Golgi vesicle and mitochondria; and biomolecules like nucleic acids and proteins are transferred through these TnTs. These TnTs are long cytoplasmic extensions made up of actin that function as intercellular bridge and connect a wide variety of cell types. Malignant cells form TnTs with either other malignant cells or cells of the surrounding tumor matrix. These TnTs help in the process of initiation of tumor formation, its organization and propagation. The current review focuses on the role of TnTs mediated cell – cell signaling in cancer micro-environment. Drugs that inhibit TnT-formation such as metformin and everolimus can be targeted towards TnTs in the management of cancer growth, proliferation, tumor invasion and metastasis.
20 December 2020 in Molecular Reproduction and Development
Purpose To identify the paternal factors responsible for aberrant embryo development leading to loss of foetus in recurrent pregnancy loss (RPL) through proteomic analysis of ejaculated spermatozoa. Materials and Methods: This prospective study consisted of male partners of RPL patients (n=16) experienced with two or more consecutive unexplained miscarriages and with no female factor abnormality as revealed by gynaecologic investigation including karyotyping and age matched fertile healthy volunteers (n-20). All samples were collected during 2013 to 2015 after getting institutional ethical approval and written consent from the participants. Seminal ejaculates were collected by masturbation after 2 to 3 days of sexual abstinence and analyzed according to World Health Organization 5th criteria 2010. Two-dimensional difference gel electrophoresis followed by mass spectrophotometric analysis was used to identify differentially expressed proteins (DEPs). Western blotting was used for validation of the key proteins. Results: The data identified 36 protein spots to be differentially expressed by more than 2-fold change with p<0.05 considered as significant. Matrix-assisted laser desorption/ionization time of flight/mass spectrometry identified GPx4, JIP4, ZN248 to be overexpressed while HSPA2, GSTM5, TF3C1, CC74A was underexpressed in RPL group. Western blot analysis confirmed the differential expression of key redox associated proteins GPx4 and HSPA2 in the RPL group. Functional analysis revealed the involvement of key biological processes that includes spermatogenesis, response to oxidative stress, protein folding and metabolic process. Conclusions: The present study provides a snapshot of the altered protein expression levels consistent with the potential involvement of the sperm chromatin landscape in early embryonic development.