What is the environment that cancer thrives on? Will our immune system help in the fight against cancer? How do we strengthen our vascular cell walls? How do we remove or fight infection/stress at the cellular level.
What are important genes that can help us in the fight against cancer? How can our body fight cancer? What is the role of authophagy in cancer development?
PDCD1 gene: This gene encodes a cell surface membrane protein of the immunoglobulin superfamily. This protein is expressed in pro-B-cells and is thought to play a role in their differentiation. In mice, expression of this gene is induced in the thymus when anti-CD3 antibodies are injected and large numbers of thymocytes undergo apoptosis. Mice deficient for this gene bred on a BALB/c background developed dilated cardiomyopathy and died from congestive heart failure. These studies suggest that this gene product may also be important in T cell function and contribute to the prevention of autoimmune diseases. [provided by RefSeq, Jul 2008]
CTLA4: This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]
CD274 gene: This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
SNCA gene: Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer’s disease. Four alternatively spliced transcripts encoding two different isoforms have been identified for this gene. [provided by RefSeq, Mar 2009]
IFNG gene: This gene encodes a soluble cytokine that is a member of the type II interferon class. The encoded protein is secreted by cells of the both the innate and adaptive immune systems. The active protein is a homodimer that binds to the interferon gamma receptor which triggers a cellular response to viral and microbial inflections. Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases. [provided by RefSeq, Sep 2015]
BCL2L11 Gene: The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]
Gene description summary is from http://www.genecards.org/Search/Keyword?queryString=PD1
Gkretsi V, Stylianou A, Papageorgis P, Polydorou C, Stylianopoulos T. Remodeling components of the tumor microenvironment to enhance cancer therapy. Front Oncol. 2015;5:214. doi:10.3389/fonc.2015.00214. 2. Nelson D, Fisher S, Robinson B. The ‘‘Trojan Horse’’ Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment. J Immunol Res. 2014;2014:789069. doi:10.1155/2014/789069.
Tumor microenvironment for cancer progression
Recent studies in the field of cancer research have shed light upon the critical role of tumor microenvironment for cancer progression, highlighted that understanding the interplay between cancer cells and their microenvironment can promote cancer pathogenesis and facilitate the development of more effective therapeutic approaches. The tumor microenvironment consists of tumor blood and lymphatic vessels and the tumor stroma. The latter contains non-cancer cells and tumor ECM components and its effects on cancer cell properties are considered pleiotropic. However, apart from regulating cancer cell behavior, abnormalities of the tumor vasculature and stroma pose barriers to the effective delivery of therapeutic agents, which can compromise treatment outcomes. Thus, understanding the tumor microenvironment and its abnormalities during cancer progression is fundamental for the development of better treatment strategies.
Tumor blood vessel hyperpermeability, and compression of intratumoral blood vessels
In this review article, we have summarized the common abnormalities observed in the tumor microenvironment, including tumor blood vessel hyperpermeability, and compression of intratumoral blood vessels due to the development of mechanical forces, as a result of stromal aberrations. We have also indicated molecules that could be used as targets in order to modulate tumor microenvironment, including angiogenic factors, such as VEGF, as well as ECM-remodeling growth factors, such as TGFβ (6). The ultimate research goal would be to make the tumor microenvironment phenotype less “cancerous” and more “normal” by targeting these molecules (165). Strategies that have been developed to normalize cancers include vessel normalization and stress alleviation techniques that can be used alone or in combination depending on tumor type (86).
86: Stylianopoulos T, Jain RK.. Combining two strategies to improve perfusion and drug delivery in solid tumors. Proc Natl Acad Sci U S A (2013) 110:18632–7.10.1073/pnas.1318415110 [PMC free article] [PubMed] [Cross Ref]
165: Jain RK.. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol (2013) 31:2205–18.10.1200/JCO.2012.46.3653 [PMC free article] [PubMed] [Cross Ref]
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