Abstract 5231: Undifferentiated cell maker rBC2LC-N lectin have high affinity to pancreatic cancer cells and residual cancer cells

Abstract

Abstract The glycosylation in cancer cells remains still unclear despite the whole human genome understanding. Recent technical advances give us great awareness about the consequence of the glycosylation. The glycomes of cancer cell surfaces are often unique with aberrant glycans, including sialylation, fucosylation, O-glycan truncation, and N-and O-linked glycan branching. The sugar binding proteins named ‘lectins’ are helpful materials to recognize the glycan structure and characterization. Recent study suggested lectins are more widely accepted that involved in many biological phenomena inside mammalian or as chemical research tools. Despite years of effort to develop cancer therapies, there were no effective molecular targeting drugs for pancreatic adenocarcinoma (PDAC). One possible reason for this difficulties, PDAC cells are densely covered with glycans which may cause the recalcitrance to approach molecular targeting drugs. Our group developed a high-density lectin microarray using 96 kinds of lectins, in which a panel well-defined lectins is immobilized onto a slide, has been successfully used for high-throughput analysis of complex carbohydrates included in serum glycoproteins and whole cells. Using this approach, we demonstrated that a recombinant lectin probe, rBC2LC-N, specifically bound to undifferentiated pluripotent stem cells (ES/iPS cells), but not differentiated somatic cells; this has now been developed as a useful undifferentiation marker. In this study, we employed this lectin microarray to investigate the specific glycan that covered pancreatic cancer cells with stem cell features. Firstly, we selected a cell line which reflect clinical PDAC cells among 6 pancreatic cancer cell lines by morphological analysis and cancer stem cell marker expressions. As previously reported, we regarded Capan-1 cell line as a closest one which maintains both self-renewal and differentiation capacity. As a result, we successfully identified top 10 highlighted lectins which have significant specificity to pancreatic cancer cells. rBC2LC-N lectin was the most significant one (P value = 9.44E-17), followed by ADA (P= 7.05E-9), TJA2 (P= 1.4E-8), ACG (P= 1.11E-6). We reconfirmed the specific reactivity of these lectins to Capan-1 by FACS and lectin histochemistry. rBC2LC-N lectin reactivity in 70 clinical cases of PDAC revealed that all cases were confirmed to be positive. Furthermore, we investigated this rBC2LC-N lectin have a high affinity to residual cancer cells after gemcitabine treatment in patient derived xenograft models. These reactions well agreed with those of undifferentiated iPS/ES cells. These coincidental match of glycan expression between on iPS/ES cells and on pancreatic cancer cells may suggest a great benefit to understand the ambiguous stem cell recognition in cancer community and novel therapeutic strategy. Citation Format: Osamu Shimomura, Tastsuya Oda, Hiroaki Tateno, Sho Tachino, Junji Matsui, Yuusuke Ozawa, Jun Hirabayashi, Nobuhiro Ohkohchi. Undifferentiated cell maker rBC2LC-N lectin have high affinity to pancreatic cancer cells and residual cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5231. doi:10.1158/1538-7445.AM2017-5231