Endothelial cells-directed angiogenesis in colorectal cancer: Interleukin as the mediator and pharmacological target.

Enhanced angiogenesis is a cancer hallmark and critical for colorectal cancer (CRC) invasion and metastasis. Upon exposure to proangiogenic factors, therefore, targeting tumor-associated proangiogenic factors/receptors hold great promise as a therapeutic modality to treat CRC, particularly metastatic CRC. Accumulating evidence from numerous studies suggests that tumor endothelial cells (ECs) are not only the target of proangiogenic factors, but also function as the cellular source of proangiogenic factors. Studies showed that ECs can produce different proangiogenic factors to participate in the regulation of angiogenesis process, in which ECs-derived interleukins (ILs) show a potential stimulatory effect on angiogenesis via either an direct action on their receptors expressed on progenitor of ECs or an indirect way through enhanced production of other proangiogenic factors. Although a great deal of attention is given to the effects of tumor-derived and immune cell-derived ILs, few studies describe the potential effects of vascular ECs-derived ILs on the tumor angiogenesis process. This review provides an updated summary of available information on proangiogenic ILs, such as IL-1, IL-6, IL-8, IL-17, IL-22, IL-33, IL-34, and IL-37, released by microvascular ECs as potential drivers of the tumor angiogenesis process and discusses their potential as a novel candidate for antiangiogenic target for the treatment of CRC patients.

Changes of immunocytic phenotypes and functions from human colorectal adenomatous stage to cancerous stage: Update.

It is believed that chronic inflammation as seen in patients with ulcerative colitis significantly increases the colorectal cancer (CRC) risk and functions as the main driving force for the development of colitis associated CRC. Recently, increasing evidences suggest that inflammation is also involved in the processing of sporadic CRCs that mostly develop from the preformed adenomas through a long-term progression. Within the adenoma/CRC tumor microenvironment, high dense immunocytes with significant phenotypic and functional changes have been observed. These cells might produce high level of inflammatory mediators and then affect the adenoma-cancer transition. In this review, we summarize the update on altered phenotypes and inflammatory mediators within the tumor microenvironment from the adenomatous stage to the cancerous stage, and discuss the significance of inflammatory mediators as biomarkers in predicating the progression from the premalignant adenoma lesion to the sporadic CRC lesion and the potential as therapeutic targets.