Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection

Abstract

Preoperative MCP-1 levels were higher in CRC patients (vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.

Plasma Levels of Keratinocyte Growth Factor Are Significantly Elevated for 5 Weeks After Minimally Invasive Colorectal Resection Which May Promote Cancer Recurrence and Metastasis

“…KGF may follow the concentration gradient from the wound (high KGF levels) to the circulation (low KGF levels). This is in keeping with many of the other proteins, mentioned above, whose plasma levels have been shown to be persistently increased after colorectal resection ( 11 , 15 , 16 , 18 , 19 , 21 – 26 ). In a study that simultaneously assessed plasma and wound fluid levels of 8 of these “long duration” proteins after colorectal resection, it was demonstrated that the mean wound levels of the proteins were 3 to 40 times higher than their corresponding plasma concentrations which, in turn, were significantly elevated from their pre-operative baseline blood levels ( 27 ).…”

“…The majority of plasma protein changes after surgery persist hours or days (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), however, in the last decade, increases in the blood levels of at least 12 proangiogenic proteins have been noted to persist for 3-5 weeks after resection of colorectal cancer (CRC). Included on this list are vascular endothelial growth factor (VEGF), angiopoeitin-2 (Ang-2), placental growth factor (PIGF), soluble vascular adhesion molecule-1 (sVCAM-1), Angiopoietin like 4 (ANPTL4), monocyte chemotactic protein-1 (MCP-1), human chitinase 3-like 1 (Chi3L1), matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-3 (MMP-7), Chemokine (C-X-C motif) ligand 16 (CXCL 16), and Interleukin 8 (IL-8).…”

“…It has been shown that the binding of sVCAM-1 to EC bound VLA4, in vitro , induces EC chemotaxis via the p38 mitogen-activated protein (MAP) kinase and focal adhesion kinase (FAK) signaling pathway which are important early step in the complex process of angiogenesis ( 18 , 49 , 50 ). MCP-1 is thought to facilitate angiogenesis via recruitment of proangiogenic protein producing monocytes and macrophages and endothelial cells into wounds and tumors ( 19 ). Macrophages in tumor stroma have been shown to express CHi3L1 which is likely to stimulate tumor angiogenesis ( 20 , 51 ).…”

“…The vast majority of plasma protein changes after surgery last hours or days (IL-1, TNF, IL-6, CRP, etc.) (12)(13)(14), however, in the last decade, increases in blood levels of at least 12 progangiogenic proteins have been noted to persist for 3 to 5 weeks after resection of colorectal cancer (CRC) (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). In vitro studies utilizing endothelial cells (EC's), critical to angiogenesis, suggest the net effect of plasma compositional changes is proangiogenic.…”

Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer

“…They are able to regulate the intensity and duration of the immune response by either stimulating or inhibiting the activation, proliferation and/or differentiation of various cells and are also able to regulate the secretion of antibodies and other cytokines[ 5 ]. By targeting selected cytokine networks or pathways one may be able to restrain CRC tumorigenesis or even improve the response rate in CRC tumours to chemotherapies, and there are several clinical trials that have focused on evaluating the blockage of different cytokines[ 6 - 8 ].…”