CD73 and cN-II regulate the cellular response to chemotherapeutic and hypoxic stress in lung adenocarcinoma cells

Abstract

Background: Cytosolic 5'-nucleotidase II (cN-II) and ecto-5'-nucleotidase (CD73) are enzymes involved in the nucleotide metabolism by dephosphorylating nucleoside monophosphates. Both enzymes are involved in cancer by modifying anticancer drug activity, cancer cell biology and immune modulation.

Methods: We have modified lung cancer cells (NCI-H292) to become deficient for either or both enzymes using the CRISPR/Cas9 technique, and studied the implication of the two enzymes in the cellular response to different stress condition i.e. chemotherapeutic agents, hypoxia and nucleotide stress.

Results: Our results show that there is no significant role of these enzymes in cell proliferation under hypoxic stress. Similarly, cN-II and CD73 are not involved in wound healing ability under CoCl₂-mediated HIF-1α stabilization. Furthermore, our results show that CD73-deficiency is associated with increased apoptosis in response to 1600 μM adenosine, decreased sensitivity to mitomycin and enhanced sensitivity to vincristine. cN-II deficiency increased in vivo tumor growth and sensitivity to vincristine and mitomycin C.

Conclusions: Our study gives new insights into the biological roles of cN-II and CD73 under stress conditions in this particular cancer cell line. Further experiments will help deciphering the molecular mechanisms underlying the observed differences.

Keywords: 5′-nucleotidase; Cancer cells; Cancer drugs; Cellular response; Hypoxia.