Abstract
Inflammation is a hallmark of colorectal cancer (CRC). Neutrophils are well-known mediators in tumor biology but their role in solid tumors, including CRC, was redefined by neutrophil extracellular traps (NETs). Given that it was recently demonstrated that platelet-derived polyP primes neutrophils to release NETs, we examined surgical specimens from CRC to investigate the presence of polyP, as a possible NET inducer. Biopsies with adenomas, hyperplastic polyps, inflammatory bowel disease and healthy colon tissues were used as controls. In all cases, the presence of polyP was apparent, with the main source of polyP being the mast cells. In all CRC and all adenomas with high-grade dysplasia, a substantial number of mast cells, more than 50%, co-expressed intracellularly polyP with CD68 surface antigen (CD68+), but this was not the case in the other examined disorders. PolyP-expressing mast cells were detected in close proximity with tumor cells and neutrophils, suggesting polyP expression by CD68+ mast cells among the stimuli which prime neutrophils to release NETs, in CRC. Moreover, the detection of CD68+ polyP-expressing mast cells could represent a potential prognostic marker in colorectal adenomas and/or carcinomas.
Highlights
Inflammation is a hallmark of solid tumors, including colorectal cancer (CRC)[1,2]
Since it has been recently indicated that neutrophil extracellular traps (NETs) are abundant in sections of human CRC[10] and considering that polyP, a naturally occurring molecule, was recently identified as a NET inducer[14], we investigated whether polyP is present in human colon adenocarcinoma
In accordance with our previous results, CD68+ polyP-expressing cells were identified only in CRC sections (S1A and S1B Fig). This is the first time that polyP was shown to be expressed by CD68+ mast cells in malignant and pre-malignant environment, namely that of colonic adenocarcinoma and adenomas with high-grade dysplasia
Summary
Inflammation is a hallmark of solid tumors, including colorectal cancer (CRC)[1,2]. It is possible that the recruitment and/or activation of inflammatory cells, such as lymphocytes, macrophages and mast cells, is defined by the tumor milieu, the way by which these cells interact with cancer cells remains ambiguous[3]. Neutrophils in particular were an understudied cell population in cancer and their implication in pathological processes was restricted mainly to infection and inflammation[4,5,6]. It has been suggested that NETs might favor metastasis[11,12] and they have been implicated in cancer-associated thrombosis[9,13]
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