Identification of a novel mechanism for meso-tetra (4-carboxyphenyl) porphyrin (TCPP) uptake in cancer cells

David J. Elzi, William E. Bauta, Jamila R. Sanchez, Trisha Das, Shweta Mogare, Peter Zannes Fatland, Moises Iza, Alexander Pertsemlidis, Vivienne I. Rebel

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere21427
JournalFASEB Journal
Volume35
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • CD320
  • cell biology
  • clathrin-dependent endocytosis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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