Abstract 4017: Dynamic biochemical tissue analysis detects functional selectin ligands expressed on breast, colorectal, liver, lung, ovarian, pancreatic, prostate, and stomach cancer tissues

Abstract

Abstract Accumulating evidence suggests that selectin/selectin ligand interactions are involved in mediating the adhesion of bloodborne circulating tumor cells at distant sites during the later stages of cancer metastasis. Presently, immunostaining is the standard method for detecting selectin ligands expressed on tissue, but this approach cannot ascertain if the selectin ligands are functional. That is, detection of purported selectin ligands by static (no-force) immunostaining under equilibrium conditions does not necessitate that the reactive antigens are able to mediate cell adhesion with hemodynamic flow (force) under non-equilibrium conditions. The relevance of functional selectin ligands as a biomarker is presently unclear because of the lack of adequate detection methods. Recently, we developed a method to detect functional selectin ligands in situ by perfusing selectin-coated microspheres (probes) over cancer tissues in a microfluidic device. This method of tissue interrogation is termed dynamic biochemical tissue analysis (DBTA). Preliminary analysis of signet ring cell colon carcinoma tissue revealed the highest amount of specific probe adhesion relative to negative control probes occurred with a murine E-selectin probe, rather than human E-, P-, or L-selectin probes. Therefore, to investigate the relevance of functional selectin ligand expression on cancer tissue as a biomarker, 196 cases of various solid tumors at primary and metastatic sites were investigated with DBTA using murine E-selectin. Probe adhesion occurred on multiple cases of breast, colon, liver, lung, ovarian, pancreatic, prostate, and stomach cancers, demonstrating the presence of functional selectin ligands. In addition, probe adhesion occurred on multiple cases of breast, colon, liver, lung, ovarian, pancreatic, rectal, and stomach cancer tissues sampled from metastatic sites. Overall, probe adhesion levels for the tissues investigated ranged from 10 specifically adherent probes/mm2 on lung adenosquamous carcinoma to 1170 specifically adherent probes/mm2 on ovarian endometrioid adenocarcinoma, indicating broad levels of functional selectin ligand expression. In summary, DBTA detects functional selectin ligands expressed on tissue from multiple cancer types at both the primary and metastatic sites, data that may provide valuable diagnostic and prognostic information for malignant tumors. Citation Format: Eric Martin, Ramiro Malgor, Douglas Goetz, Monica Burdick. Dynamic biochemical tissue analysis detects functional selectin ligands expressed on breast, colorectal, liver, lung, ovarian, pancreatic, prostate, and stomach cancer tissues. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4017. doi:10.1158/1538-7445.AM2014-4017