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NIH Research Festival

September 13 – 15, 2017

CD38 knockout suppresses tumorigenesis in mice and clonogenic growth of human lung cancer cells

Friday, September 15, 2017 – Poster Session IV
1:00 – 2:30 p.m.

FAES Terrace

NHLBI

CANCER-16

Authors

  • X Bu
  • J Kato
  • JA Hong
  • MJ Merino
  • DS Schrump
  • FE Lund
  • J Moss

Abstract

The ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development in multiple organs. In the present study, we found that in wild-type and ARH1-deficient mice deletion of the CD38 gene reduced tumor formation. Significant reductions in tumor number were observed in ARH1/CD38 double knockout mice compared to ARH1-deficent mice and in CD38 knockout mice compared to in wild-type mice. Consistent with a role for CD38 in tumorigenesis, knockout of CD38 in A549 human adenocarcinoma cells inhibited anchorage-independent cell growth, cell invasion and xenograft growth in nude mice. CD38 mRNA and protein expression were evaluated in human lung cancer cell lines and in human lung cancer specimens. CD38-positive tumor cells were identified in 11 of 27 patient samples. In addition, some human lung cancer cell lines had dramatically higher CD38 mRNA and protein expression than normal cells. Search of the Oncomine database showed that some human lung adenocarcinomas had higher CD38 mRNA levels compared to normal lung tissues. In total, we demonstrated that CD38 plays a role in murine and human lung tumorigenesis and that anti-CD38 treatment may have therapeutic potential in lung cancer.

Scientific Focus Area: Cancer Biology

This page was last updated on Friday, March 26, 2021

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Current Research Festival

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  • 2024
    • General Schedule of Events
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