Maspin expression in prostate tumor elicits host anti-tumor immunity.
The goal of the current study is to examine the biological effects of epithelial-specific tumor suppressor maspin on tumor host immune response. Accumulated evidence demonstrates an anti-tumor effect of maspin on tumor growth, invasion and metastasis. The molecular mechanism underlying these biological functions of maspin is thought to be through histone deacetylase inhibition, key to the maintenance of differentiated epithelial phenotype. Since tumor-driven stromal reactivities co-evolve in tumor progression and metastasis, it is not surprising that maspin expression in tumor cells inhibits extracellular matrix degradation, increases fibrosis and blocks hypoxia-induced angiogenesis. Using the athymic nude mouse model capable of supporting the growth and progression of xenogeneic human prostate cancer cells, we further demonstrate that maspin expression in tumor cells elicits neutrophil- and B cells-dependent host tumor immunogenicity. Specifically, mice bearing maspin-expressing tumors exhibited increased systemic and intratumoral neutrophil maturation, activation and antibody-dependent cytotoxicity, and decreased peritumoral lymphangiogenesis. These results reveal a novel biological function of maspin in directing host immunity towards tumor elimination that helps explain the significant reduction of xenograft tumor incidence in vivo and the clinical correlation of maspin with better prognosis of several types of cancer. Taken together, our data raised the possibility for novel maspin-based cancer immunotherapies.
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Sijana H
SH
Dzinic
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan. Department of Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Detroit, Michigan. Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland.
Kang
K
Chen
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Archana
A
Thakur
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Current address: BIOBASE Corporation, Beverly, Massachusetts.
Alexander
A
Kaplun
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Urology, Wayne State University School of Medicine, Detroit, Michigan.
R Daniel
RD
Bonfil
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Xiaohua
X
Li
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Jason
J
Liu
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
M Margarida
MM
Bernardo
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Urology, Wayne State University School of Medicine, Detroit, Michigan.
Allen
A
Saliganan
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Jessica B
JB
Back
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Hiroshi
H
Yano
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Dana L
DL
Schalk
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Elyse N
EN
Tomaszewski
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Ahmed S
AS
Beydoun
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Gregory
G
Dyson
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Adelina
A
Mujagic
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
David
D
Krass
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Ivory
I
Dean
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan. Henry Ford Health Systems, Detroit, Michigan.
Qing-Sheng
QS
Mi
Department of Urology, Wayne State University School of Medicine, Detroit, Michigan. Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Elisabeth
E
Heath
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Wael
W
Sakr
Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan. Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan.
Lawrence G
LG
Lum
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Shijie
S
Sheng
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015843:Serpins / Q000096:biosynthesis / Q000276:immunology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
C085344:SERPIN-B5; D015843:Serpins