Monoclonal Antibody against CXCL1 (HL2401) as a Novel Agent in Suppressing IL6 Expression and Tumoral Growth

Theranostics
Makito MiyakeCharles J Rosser

Abstract

Rationale: The expression of the chemokine (C-X-C motif) ligand 1 (CXCL1), an inflammatory protein, has been reported to be up-regulated in many human cancers. The mechanisms through which aberrant cellular CXCL1 levels promote specific steps in tumor growth and progression are unknown. Methods: We described the anticancer effects and mechanism of action of HL2401, a monoclonal antibody directed at CXCL1 with in vitro and in vivo data on bladder and prostate cancers. Results: HL2401 inhibited proliferation and invasion of bladder and prostate cells along with disrupting endothelial sprouting in vitro. Furthermore, novel mechanistic investigations revealed that CXCL1 expression stimulated interleukin 6 (IL6) expression and repressed tissue inhibitor of metalloproteinase 4 (TIMP4). Systemic administration of HL2401 in mice bearing bladder and prostate xenograft tumors retarded tumor growth through the inhibition of cellular proliferation and angiogenesis along with an induction of apoptosis. Our findings reveal a previously undocumented relationship between CXCL1, IL6 and TIMP4 in solid tumor biology. Principal conclusions: Taken together, our results argue that CXCL1 plays an important role in sustaining the growth of bladder an...Continue Reading

Citations

Aug 20, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Bao YangTianke Li
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chao WangAh-Ng Kong
Oct 2, 2020·Viruses·Nedaa Alomari, Jennifer Totonchy
Jan 21, 2021·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Jul 12, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Bowen YangZhiyu Wang
Oct 10, 2021·Advanced Healthcare Materials·Zhaoyu MaHeyou Han

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Methods Mentioned

BETA
xenograft
ELISA
PCR
antibody array
immunoprecipitation
xenografts
protein assay
transfection

Software Mentioned

WinNonLin
GraphPad
Inveon Research Workplace
ImageJ
Origene
GraphPad Prism

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