Journal of the Federation of Societies for the Study of Experimental Biology (FASEB Journal), Feb. 25, 2021

 
Authors
David J. Elzi, William E. Bauta, Jamila R. Sanchez, Trisha Das, Shweta Mogare, Peter Zannes Fatland, Moises Iza, Alexander Pertsemlidis, Vivienne I. Rebel
 
Description
The paper explains research that identified a novel mechanism by which the porphyrin TCPP, which is used in bioAffinity Technologies’ non-invasive test for the early detection of lung cancer, is incorporated into cancer cells using the cellular receptor CD320, which is involved in the uptake of Vitamin B12. In addition to furthering the understanding of TCPP for use in diagnostics, bioAffinity’s research led to four patent applications protecting multiple novel therapeutic platforms for treating cancer.
 
Abstract
Porphyrins are used for cancer diagnostic and therapeutic applications, but the mechanism of how porphyrins accumulate in cancer cells remains elusive. Knowledge of how porphyrins enter cancer cells can aid the development of more accurate cancer diagnostics and therapeutics. To gain insight into porphyrin uptake mechanisms in cancer cells, we developed a flow cytometry assay to quantify cellular uptake of meso-tetra (4-carboxyphenyl) porphyrin (TCPP), a porphyrin that is currently being developed for cancer diagnostics. We found that TCPP enters cancer cells through clathrin-mediated endocytosis.

The LDL receptor, previously implicated in the cellular uptake of other porphyrins, only contributes modestly to uptake. We report that TCPP instead binds strongly ((Formula presented.)) to CD320, the cellular receptor for cobalamin/transcobalamin II (Cbl/TCN2). Additionally, TCPP competes with Cbl/TCN2 for CD320 binding, suggesting that CD320 is a novel receptor for TCPP. Knockdown of CD320 inhibits TCPP uptake by up to 40% in multiple cancer cell lines, including lung, breast, and prostate cell lines, which supports our hypothesis that CD320 both binds to and transports TCPP into cancer cells. Our findings provide some novel insights into why porphyrins concentrate in cancer cells. Additionally, our study describes a novel function for the CD320 receptor which has been reported to transport only Cbl/TCN2 complexes.