Abstracts Category : Other

Adhesion Based Early Detection of Colorectal Cancer

by Sarah J Bodle

Colorectal cancer (CRC) is the fourth most diagnosedcancer and the second leading cause of cancer death with 135,430new cases and 50,260 deaths predicted to occur in the United Statesin 2017 Cancer Statistics Center, ACS Available:http://cancerstatisticscenter.cancer.org/. With current screeningtests, the percentage of diagnosis occurring at localized,regional, distant, and unknown stages are 39, 35, 21, and 5 percentwith corresponding 5-year survival rates of 90.1, 71.2, 13.5, and35.5 percent, respectively Cancer of the Colon and Rectum - CancerStat Facts, NCI Available:https://seer.cancer.gov/statfacts/html/colorect.html. The highmortality rate can be attributed to the percentage of later stagediagnosis. As such, there is a demand for novel diagnostics thatincrease the percentage of diagnosis occurring at an early stagewhen the survival rate is most promising. It is possible that anovel diagnostic could be designed based on the increasedexpression of adhesion molecules on transforming tissue relative tonormal tissue. Transforming tissue would be identified by detectionconstructs consisting of microparticles conjugated to ligandscognate to the adhesion molecules. The detection constructs wouldbe administered to the epithelium of the colorectum via a spraycatheter through the biopsy channel of an endoscope duringcolonoscopy.The broad working hypothesis of this study is thatdifferential expression of adhesion molecules on transforming andcancerous, relative to normal tissue, can be exploited to develop aligand conjugated particle based in situ diagnostic assay. As afirst step, the goal of this thesis was to characterize theexpression of sialyl Lewis A (sLeA), sialyl Lewis X (sLeX), andCD44 on transforming and cancerous, relative to normal, cell linesand tissues.Expression levels of CD44 proteins as well as sLeA andsLeX glycans on cancerous relative to normal human colorectal celllines were quantified by flow cytometry. This analysis revealedthat CD44v3 and CD44v5 proteins have increased expression oncancerous relative to normal human colorectal cell lines whenidentified by anti- CD44v3 mAb 3G5 and anti- CD44v5 mAb VFF-8. Inaddition, sLeA and sLeX glycans have increased expression oncancerous relative to normal human colorectal cell lines whenidentified by anti- sLeA mAb KM231, anti- sLeA mAb C241:5:1:4,anti- sLeX mAb CSLEX1, anti- sLeX mAb FH6, and anti- cutaneouslymphocyte antigen (CLA) mAb HECA-452. Expression levels of sLeAand sLeX were characterized on human colorectal tissues byimmunohistochemistry. The average percent staining of each core forsLeA is significantly lower on normal tissues and normal adjacenttissues compared to stage I adenocarcinoma tissues when identifiedby anti- sLeA mAb KM231 and anti- sLeA mAb C241:5:1:4. Results alsoshow the average percent of staining of each tissue core for sLeXis significantly lower on normal tissues and normal adjacenttissues compared to stage I adenocarcinoma tissues when identifiedby anti- sLeX mAb CSLEX1. Anti- CLAAdvisors/Committee Members: Goetz, Douglas (Advisor).