Immunization against hyaluronidase Hyal‐2 provides long‐term cancer prevention
Abstract
When immune deficient or competent mice were pre‐injected with micromolar levels of Zfra (a 31‐amino‐acid zinc finger‐like protein), these mice acquired a long‐term resistance to the growth and metastasis of a broad spectrum of cancer xenografts. Injected Zfra is accumulated mainly in the spleen, and, accordingly, the induced anticancer response is memorized and can be transferred to naïve immune‐deficient mice via spleen cells. Alteration of the Ser8 phosphorylation site to Gly8 abolished Zfra polymerization and cancer prevention in vivo. Zfra suppresses the activation of tumor suppressor WWOX (FOR or WOX1) and the expression of hyaluronidase Hyal‐2 in the spleen. Likewise, antibody against Hyal‐2 or activated WWOX mimics and dramatically boosts the anticancer effect of Zfra. Mechanistically, Zfra binds and activates non‐T/non‐B memory Hyal‐2+ spleen cells, via Hyal‐2/WWOX/Smad4 signaling, for conferring a long‐term protection against cancer growth and metastasis in vivo. (Supported in part by NHRI and DOD, Taiwan, and DoD, USA)
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2013
- Source ID
- 10.1096/fasebj.27.1_supplement.592.4
Entities
People
- Nan‐shan Chang
- Wan‐pei Su
Organizations
- National Cheng Kung University
- National Health Research Institutes
- United States Department of Defense