Matrix Metalloproteinases and Stress Hormones in Lung Cancer Progression.

Several matrix metalloproteinases (MMPs) and psychological stress are associated with poor cancer prognosis. The current work goal was to determine MMPs' and stress hormones' blood concentrations from lung adenocarcinoma (LAC) patients. Patients were divided into the following groups: tobacco smokers (TS), wood smoke-exposed (W), passive smokers (PS), TS exposed to wood smoke (TW), and patients with no recognizable risk factor (N). MMPs, tissue inhibitors of metalloproteinases (TIMPs), adrenaline, noradrenaline, and cortisol blood concentrations were measured by ELISA. Zymography and Western blot assays were performed to determine MMP-2 and MMP-9 active and latent forms. MMP-2, MMP-3, MMP-9, and TIMP-1 blood concentrations, and MMP-9 gelatinase activity were augmented, while MMP-12, MMP-14, and TIMP-2 were diminished in LAC patients. Cortisol was increased in LAC samples. Adrenaline concentrations were higher in W, TS, and TW, and noradrenaline was increased in W and N groups. Positive correlations were observed among cortisol and TIMP-1 (r s = 0.392) and TIMP-2 (r s = 0.409) in the W group and between noradrenaline and MMP-2 (r s = 0.391) in the N group. MMPs' blood concentration increments can be considered as lung cancer progression markers. Although stress hormones were also augmented, only weak correlations were observed between them and MMPs and TIMPs.

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs' augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhibitors have been created to block MMPs' enzymatic activity. However, they have been ineffective in addition to causing considerable side effects. On the other hand, nanotechnology offers the opportunity to formulate therapeutic agents that can act directly on a target cell, avoiding side effects and improving the diagnosis, follow-up, and treatment of cancer. The goal of the present review is to discuss novel nanotechnological strategies in which MMPs are used with theranostic purposes and as therapeutic targets to control cancer progression.

Matrix Metalloproteinases' Role in Tumor Microenvironment.

Cancer cells evolve in the tumor microenvironment (TME) by the acquisition of characteristics that allow them to initiate their passage through a series of events that constitute the metastatic cascade. For this purpose, tumor cells maintain a crosstalk with TME non-neoplastic cells transforming them into their allies. "Corrupted" cells such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs) as well as neoplastic cells express and secrete matrix metalloproteinases (MMPs). Moreover, TME metabolic conditions such as hypoxia and acidification induce MMPs' synthesis in both cancer and stromal cells. MMPs' participation in TME consists in promoting events, for example, epithelial-mesenchymal transition (EMT), apoptosis resistance, angiogenesis, and lymphangiogenesis. MMPs also facilitate tumor cell migration through the basement membrane (BM) and extracellular matrix (ECM). The aim of the present chapter is to discuss MMPs' contribution to the evolution of cancer cells, their cellular origin, and their influence in the main processes that take place in the TME.

Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer.

Matrix metalloproteinases (MMPs) participate from the initial phases of cancer onset to the settlement of a metastatic niche in a second organ. Their role in cancer progression is related to their involvement in the extracellular matrix (ECM) degradation and in the regulation and processing of adhesion and cytoskeletal proteins, growth factors, chemokines and cytokines. MMPs participation in cancer progression makes them an attractive target for cancer therapy. MMPs have also been used for theranostic purposes in the detection of primary tumor and metastatic tissue in which a particular MMP is overexpressed, to follow up on therapy responses, and in the activation of cancer cytotoxic pro-drugs as part of nano-delivery-systems that increase drug concentration in a specific tumor target. Herein, we review MMPs molecular characteristics, their synthesis regulation and enzymatic activity, their participation in the metastatic process, and how their functions have been used to improve cancer treatment.