Abstract
Many cellular functions important for solid tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell attachment receptors. With recent studies emphasizing the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that considerable attention is being paid to integrins. Several integrin antagonists are under clinical trials, with many demonstrating promising activity in patients with different cancers. A deeper knowledge of the functions of integrins within the TME is still required and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This expert review offers the latest synthesis in terms of the current knowledge of integrins functions within the TME and as potential molecular targets for cancer therapeutics innovation.
Highlights
Tumorigenesis involves the transformation of normal cells into cancer cells via mechanisms that include activation of many signaling cascades
ITGβ6 expression was upregulated in CESC and esophageal carcinoma (ESCA) tumor tissues versus adjacent normal tissues whilst ITGβ6 expression showed no significant differences in head and neck squamous cell carcinoma (HNSC) and lung adenocarcinoma (LUAD) tumor tissues versus adjacent normal tissues (Figure 5B)
Whilst most cells within the human body express integrins, those expressed by tumor cells and stromal cells within the tumor microenvironment (TME) are involved in several processes along the tumorigenic path
Summary
Tumorigenesis involves the transformation of normal cells into cancer cells via mechanisms that include activation of many signaling cascades. Several studies have shown that integrins are directly involved in tumor initiation and progression via influencing cancer cell proliferation, migration, invasion and survival as well as partaking in cellular signaling [1, 2]. Beside integrins found on cancer cells, integrins are present on cells associated with tumors and play a great role in influencing stromal cell-tumour cell interactions [12,13,14] These stromal cells range from cancer associated-fibroblasts (CAFs), -macrophages (CAMs), -endothelial cells (CANs) as well as pericytes [15,16,17,18]. Integrins relay extracellular cues through receptors for growth factors and cytokines and promote cellular signaling Being present in both cancer cells and stromal cells, integrins influence tumor development as well as metastasis. The success demonstrated with integrin inhibitors must be augmented by further research into the role of integrins in different cancers as well as in tumor development and growth
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