Published online Mar 15, 2019. doi: 10.4251/wjgo.v11.i3.195
Peer-review started: October 26, 2018
First decision: November 14, 2018
Revised: January 3, 2019
Accepted: January 8, 2019
Article in press: January 9, 2019
Published online: March 15, 2019
Processing time: 140 Days and 19.2 Hours
Traditionally, immunoglobulin (Ig) was believed to be only produced by B cells; however, studies from our group and others have revealed that except B cells, most of non B cells, especially the non B cancer cells, including the colon cancer cells, can frequently express Ig (non B-Ig). According to our previous findings, cancer cell-derived IgG can significantly promote cancer initiation, progression and metastasis by promoting cancer stem cell behavior. IgG overexpression predicts poor prognosis of patients with cancer. Furthermore, comparing to the B cell-derived Ig repertoire, the non B cancer cell-derived Ig displays restricted and conservative V(D)J pattern rather than diversity. However, we do not know if the colon cancer cell-derived Ig is structurally different from its counterpart normal epithelial cell-derived Ig.
In our previous work, we have found that colon cancer cells can overexpress the IgG compared to normal colonic epithelial cells, but it remains unclear if the colon cancer cell-derived Ig repertoire display unique feature compared to its counterpart normal cell-derived Ig, and whether the unique feature is potential for colon cancer target therapy.
In this study, we used Ig repertoire sequencing (IR-Seq), which allows for the sequencing of millions of V(D)J sequences in parallel, to investigate the Ig repertoire features expressed in human colon cancer cells.
We first sorted EPCAM+ colon cancer cells and EPCAM+ normal colonic epithelial cells from corresponding noncancerous tissues as control. Then, using IR-Seq, the expression profile of Ig, VHDJH gene usage of Ig heavy chain (IgH) and somatic hypermutation (SHM) feature in Ig variable region were detected.
We surprisingly found that comparing to the control normal cells, Ig expressed by colon cancer cells had a significant tendency to choose IgG among the five Ig classes. Furthermore, unlike B-Ig that can generate nearly great diversity, the non B-Ig from either colon cancer or normal epithelial cells showed restricted VHDJH rearrangement patterns. However, comparing to normal cell-derived VHDJH rearrangement patterns, cancer cell-derived VHDJH patterns displayed unique feature, including the usage of VH, D and JH gene, and the SHM feature.
We found that colon cancer cells could frequently express IgG and unique IgH repertoires, which may be involved in carcinogenesis of colon cancer. The unique IgH repertoire has the potential to be used as a novel target in immune therapy for colon cancer.
These findings suggest that distinguishing the distinctive mutation sites of cancer cell-derived Ig from normal cell-derived Ig can help finding new target for precise treatment of patients with colon cancer.