Relationship between tumor microenviroment and development and progression of cancer: A Review

Background: Development of cancer is a multistep process in which somatic cells first undergo an initiating event (i.e., environmental insult) and then a second or promoting event. Both events accumulate genetic modifications. Tumor microenvironment is the product of developing crosstalk between different cells types. For instance, in epithelial tumors these cells include the invasive carcinoma and its stromal elements. Critical stromal elements include cancer-associated fibroblasts, which provide an essential communication network via secretion of growth factors and chemokines, inducing an altered extracellular matrix (ECM) thus providing additional oncogenic signals enhancing cancer-cell proliferation and invasion. The tumor microenvironment contributes to tumour heterogeneity. It plays crucial role in initiation, progression and metastasis of tumor by promoting tumor angiogenesis and inducing peripheral immune tolerance. It’s essential to understand tumor biology to improve molecular diagnostics and therapeutics for the future. Methods: Our study emphasizes on the role of tumor microenvironment in initiation and progression of cancer and the role of hypoxia, macrophages, and lymphocytes in its development. It focuses on approaches to prepare and analyse secreted proteins and contribution of those secreted proteins in tumor progression and identification of secreted biomarkers as the potential molecular targets for cancer therapy. Results: Tumor microenviroment is an integral part of its physiology, structure, and function. A fundamental deranged relationship between tumor and stromal cells is essential for tumor cell growth, progression, and development of life threatening metastasis. Improved understanding of this interaction may provide useful therapeutic targets for cancer management like integrins and chemokines as well as risk and recurrence assessment and prevention. Proteases expressed in the extracellular milieu, particularly matrix metalloproteinases can target ECM proteins and non-ECM proteins such as growth factors, cytokines, cell associated molecules and growth factor receptors. Therefore the activity of these proteases in tumors is very complex and includes tumor promoting as well as tumor suppressive effects. The balance between proteases and protease inhibitors is a vital determinant in cancer development because both an absence and an excess of proteolysis could have a negative effect on angiogenesis. Targeting intratumoral TAMs and MDSCs can also reduce tumor burdens by slowing angiogenesis. Non-malignant cells and secreted proteins from tumor and stromal cells are active participants in cancer progression. Conclusions: The identification and targeting of proteins secreted by cancer cells into the tumor microenvironment remains relatively unexplored. Secreted protein signatures in cancer provide important information that may be an aid to earlier diagnosis, improved disease monitoring as well as enhanced assessment of the efficacy of therapy along with rationale for required revisions of therapy. Targeting the tumor microenvironment via molecular and cellular profiles in tumor progression would be crucial for identifying cell or protein targets for cancer prevention and therapy. Clinical trial identification: GMC2591IND16 Legal entity responsible for the study: Gandhi Medical College, Bhopal Funding: Gandhi Medical College, Bhopal Disclosure: All authors have declared no conflicts of interest.