Zfra activates memory Hyal-2+ CD3- CD19- spleen cells to block cancer growth, stemness, and metastasis in vivo

Ming Hui Lee, Wan Pei Su, Wan Jen Wang, Sing Ru Lin, Chen Yu Lu, Yu An Chen, Jean Yun Chang, Shenq Shyang Huang, Pei Yi Chou, Siou Ru Ye, Szu Jung Chen, Huan He, Ting Hsiu Liu, Ying Tsen Chou, Li Jin Hsu, Feng Jie Lai, Shean Jen Chen, Hoong Chien Lee, David Kakhniashvili, Steven R. GoodmanNan Shan Chang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Zfra is a 31-amino-acid zinc finger-like protein, which participates in the tumor necrosis factor signaling. Here, we determined that when nude mice and BALB/c mice were pre-injected with nanogram levels of a synthetic Zfra1-31 or truncated Zfra4-10 peptide via tail veins, these mice became resistant to the growth, metastasis and stemness of melanoma cells, and many malignant cancer cells. The synthetic peptides underwent self-polymerization in phosphate-buffered saline. Alteration of the Ser8 phosphorylation site to Gly8 abolished Zfra aggregation and its-mediated cancer suppression in vivo. Injected Zfra peptide autofluoresced due to polymerization and was trapped mainly in the spleen. Transfer of Zfra-stimulated spleen cells to naïve mice conferred resistance to cancer growth. Zfra-binding cells, designated Hyal-2+ CD3- CD19- Z cells, are approximately 25-30% in the normal spleen, but are significantly downregulated (near 0-3%) in tumor-growing mice. Zfra prevented the loss of Z cells caused by tumors. In vitro stimulation or education of naïve spleen cells with Zfra allowed generation of activated Z cells to confer a memory anticancer response in naïve or cancer-growing mice. In particular, Z cells are abundant in nude and NOD-SCID mice, and can be readily activated by Zfra to mount against cancer growth.

Original languageEnglish
Pages (from-to)3737-3751
Number of pages15
JournalOncotarget
Volume6
Issue number6
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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