Lab : Culturing Escherichia Coli Involving Cav1.2, Connexin 43, And N Cadherin

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

Cancer is listed as the second most common cause of death in western countries; particularly, in adults. Though it has a long antiquity, its prevalence and incidence today is pervasive and the war on cancer has not been promising. Malignant neoplasia is characterized by uncontrolled growth and the ability to metastasize or spread from the original site. Cancer results from mutations that promote cell proliferation and inhibit cell adhesion (metastasis). According to the National Cancer Institute (2016), “Cancer can also spread regionally,

Even though they did not discover the precise mechanisms engaged, the investigators think the makeup of the NETs allows cancer cells migrate via tissue by literally consuming through the protein-scaffolding that forms the tissue framework. They recommend the NETs develop small gaps and crevices for the cancer cells, thus assisting to promote new colonies away from the primary tumor.

such examples include IL1, IL6, IL10, PGE2, TGF-β, VGEF, MCSF, MIF & GM-CSF (Saskia J. A. M. Santegoets, 2016). VEGF exerts a variety of effects on vascular endothelial cells which promotes the formation and growth of new blood vessels. VEGF induces calcium transients, which causes stimulation of endothelial cells, which leads them to migrate and divide. Tumour cells are also capable of ‘shedding’ alarm proteins, such as MHC-1 complex, which as a result can have a dampening effect on NKG2D mediated activation of T cells/NK cells (Saskia J. A. M. Santegoets, 2016). As chemokines, matrix metalloproteases (MMP’s), DNA, RNA and exosomes are all highly soluble, they can not only operate within the tumour microenvironment (TME), but can enter the circulation, and subsequently effect distant mediators, such as bone marrow or lymph nodes, which can in turn suppress immune response.

The first mode of action is when galectin-8 is in a high concentrations or when it is overexpressed. This induces the accumulation of p21. The next mode of action is when it is in the presence of selected growth factors and therefore immobilized. In this mode, galectin-8 has interactions with high affinity receptors. These interactions promote cell adhesion, cell spreading, and cell migration [6]. The last mode of action takes place under the conditions that there is no p21 or after continual lack of growth factors. This is when apoptosis takes place [6]. All three of these modes of action are controlled by different signaling pathways

Cancer is defined as unregulated growth of cells that deviate from usual cellular activities (NIH, 2015). This includes the development of tumors and eventually the invasion of other tissues. Metastasis of tumor cell undergoes multiple steps: invasion, intravasation, extravasation, survival and proliferation (Sethi & Kang, 2011; Van Zijl, Krupitza, & Mikulits, 2011). As GJPs have been described to provide a conduit for intracellular communication, it has been shown in many reports where connexin channels provided the means of initial metastatic lesion formation to the vasculature. Once the metastatic tumor cells invade into the blood circulation (intravasation), these cells will then be able to spread to other locations (i.e. from the breast to the brain).

SDF-1, also knows as CXCL12, is a homeostatic chemokines, whose major function is in regulating hematopoietic cell trafficking and secondary lymphoid tissue architecture. CXCR4 is normally expressed on many cell types including lymphocytes, hematopoietic stem cells, endothelial and epithelial cells [8]. Besides, CXCR4 is also the chemokine receptor most commonly expressed in tumor cells such as osteosarcoma cells. Several studies had demonstrated CXCR4 is involved in tumor cell proliferation, migration and

Neovascularization is closely involved in tumor survival, progression, and spread, - factors known to contribute significantly to the difficulties in cancer treatment. Folkman (1971) presumed that survival and proliferation of cancer depend on angiogenesis, which could be a target of cancer therapy. Similar to embryos, any tumor intending to grow bigger than 2 mm, needs functional blood vessels. According to Folkman, tumors can initially grow by capturing oxygen and nutrition via diffusion from the surrounding microenvironment, but they cannot grow beyond 2 mm without angiogenesis. The mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic

Furthermore, Hedgehog Signalling Pathway in the malignant tumor cells plays a key role in aggravating the disease. Activation of Hedgehog Pathway leads to metastasis through various mechanisms like increase in protein expression, angiogenesis etc. Hedgehog signalling begins in the stroma cells. Stroma cells are dense supporting tissue, it consists of fibroblasts, pancreatic stellate cells (PSCs) and extracellular matrix proteins, collagens I and III and fibronectin. It influences the biological properties of the tumor. It has been proven in previous in-vivo studies that the PSC’s promoted tumor growth and metastasis through cell proliferation, migration, invasion and colony formation in dose-dependent manner. Hedgehog Signalling remains inactive

TRPC6, along with other relevant adhesion molecules such as PECAM and CD99, was found to localize strongly at junctional sites where there are transmigrating leukocytes. To answer whether this bears significance, independent experiments allowing polystyrene beads coated with relevant adhesion proteins to interact with an endothelial surface were conducted, finding that the ~35% of anti-PECAM coated beads specifically recruited TRPC6. In conditions where PECAM is blocked, TRPC6 activation, subsequent ↑[Ca2+]i,, and TEM was rescued by use of intermediates in the PECAM and TRPC6 signaling pathway. A generalized ↑[Ca2+]i induced by histamine failed to promote TEM, indicating that it is likely

Acquisition of the Mesenchymal phenotype is functionally associated with the ability to overcome anoikis /another process involved in anoikis resistance is EMT which is an essential feature that allows epithelial cells participate in physiological process like embryogenesis. EMT in cancer cells / also cancer cells acquire Mesenchymal feature which allow/permit them to overcome anoikis and become motile and metastatic/in this process, cancer cells launch chain of event that enable them to acquire Mesenchymal feature and overcome anoikis. During EMT cancer cell downregulate cell-adhesion molecules like E-cadherin and γ-catenin, and increase Mesenchymal associated markers such as fibronectin and

Cancer is one of the most dangerous and fatal diseases, which is caused by uncontrolled growth and proliferation of cells. Cancer cells’ survival, progression and metastasis are tightly associated with the cellular components. For example, when cells metastasizing, they use cell protrusion which provided by the actin cytoskeleton to penetrate the extracellular matrix, they also secrete plasminogen activator to increase protease plasmin’s activity in order to penetrate the membrane. Then some of the tumor cells transfer to other tissue and form metastatic tumor. The specific functions of several cell structures and transporters in tumor cells are discussed as follows.

Epithelial cells (ECs) are the structural unit of epithelium, a tissue type that is responsible for lining the inner and outer surfaces of the body, as well as formation of many glands [1]. ECs are polarized, with the apical surface facing the lumen and the basal surface anchoring to a specialized extracellular matrix (ECM) layer, known as the basal lamina or basement membrane which separates epithelial cells from underlying tissues (Fig. 1). To maintain the physical and functional integrity of the epithelium, ECs are also laterally linked to one another through cell-to-cell adhesion molecules (CAM), most importantly, members of the cadherin family [2]. As a result, ECs within an ordinary epithelium have very limited mobility. Nevertheless, non-pathological epithelial plasticity does occur, for example, in neurulation – an important morphogenetic movement during embryogenesis [3]. Under these circumstances, ECs tend to move in concert and the integrity of the whole epithelium is not compromised [4].

The afore mentioned intricate network of interactions during EMT leads to many important changes in the phenotype and behavior of the cells. Epithelial cells undergo prominent morphological changes including the loss of cell-cell adhesion and the loss of apical-basal polarity. The cobblestone-like monolayer of epithelial cells with an apical-basal polarity is converted to dispersed, spindle-shaped mesenchymal cells with migratory protrusions. In addition to these morphological changes, cells undergoing EMT loose the expression of E-cadherin and other epithelial differentiation markers and gain the expression of mesenchymal markers such as vimentin, N-cadherin and fibronectin. These changes lead to the acquisition of migratory and invasive properties which enable the cells to migrate and invade through the ECM and the adjacent stroma (Boyer and Thiery, 1993). Thus, during cancer progression the EMT confers all the traits to the carcinoma cells which are required to overcome natural tissue barriers on their way to metastasis formation. These gained traits go hand in hand with a reduced proliferative potential of the mesenchymal-like tumor cells (Vega et al., 2004).

The impersonating behavior of tumor cells result in heterotypic signaling thereupon making cancer cell hyper-responsive to encourage more growth. Furthermore, the article suggests that in 25% human tumor cells, a Ras protein is often found structurally altered. A problem with mutated Ras protein is that it cannot be phosphorylated hence a prolonged signaling is expected. Despite knowing this, there is a limitation as to what other growth factors get deregulated in human tumor. For example, one study found that half of the tumors in human colon carcinomas bear mutant ras oncogenes (Kinzler and Vogelstein, 1996, p. 59). Thus, the researchers theorized that other half of tumor cell carried defects in growth signaling