Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis

Allison P. Watson, Rick L. Evans, Kristi A. Egland

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Routinely used therapies are not adequate to treat the heterogeneity of breast cancer, and consequently, more therapeutic targets are desperately needed. To identify novel targets, we generated a breast cancer cDNA library enriched for genes that encode membrane and secreted proteins. From this library we identified SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein containing a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies describe the mouse homolog, Susd2, but there are no studies on the human gene associated with breast cancer. Immunohistochemical analysis of human breast tissues showed weak or no expression of SUSD2 in normal epithelial cells, with the endothelial lining of vessels staining positive for SUSD2. However, staining was observed in pathologic breast lesions and in lobular and ductal carcinomas. SUSD2 interacts with galectin-1 (Gal-1), a 14-kDa secreted protein that is synthesized by carcinoma cells and promotes tumor immune evasion, angiogenesis, and metastasis. Interestingly, we found that localization of Gal-1 on the surface of cells is dependent on the presence of SUSD2. Various phenotype assays indicate that SUSD2 increases the invasion of breast cancer cells and contributes to a potential immune evasion mechanism through induction of apoptosis of Jurkat T cells. Using a syngeneic mouse model, we observed accelerated tumor formation and decreased survival in mice with tumors expressing Susd2. We found significantly fewer CD4 tumor infiltrating lymphocytes in mice with tumors expressing Susd2. Together, our findings provide evidence that SUSD2 may represent a promising therapeutic target for breast cancer.

Original languageEnglish (US)
Pages (from-to)74-85
Number of pages12
JournalMolecular Cancer Research
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Carcinogenesis
Breast
Breast Neoplasms
Galectin 1
Staining and Labeling
Tumor Escape
Tumor-Infiltrating Lymphocytes
Immune Evasion
Lobular Carcinoma
Neoplasms
Ductal Carcinoma
Jurkat Cells
Gene Library
Genes
Libraries
Membrane Proteins
Proteins
Therapeutics
Epithelial Cells
Apoptosis

Cite this

Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis. / Watson, Allison P.; Evans, Rick L.; Egland, Kristi A.

In: Molecular Cancer Research, Vol. 11, No. 1, 01.01.2013, p. 74-85.

Research output: Contribution to journalArticle

@article{5c084a8302cc4960b28fe6aa324ba0f0,
title = "Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis",
abstract = "Routinely used therapies are not adequate to treat the heterogeneity of breast cancer, and consequently, more therapeutic targets are desperately needed. To identify novel targets, we generated a breast cancer cDNA library enriched for genes that encode membrane and secreted proteins. From this library we identified SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein containing a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies describe the mouse homolog, Susd2, but there are no studies on the human gene associated with breast cancer. Immunohistochemical analysis of human breast tissues showed weak or no expression of SUSD2 in normal epithelial cells, with the endothelial lining of vessels staining positive for SUSD2. However, staining was observed in pathologic breast lesions and in lobular and ductal carcinomas. SUSD2 interacts with galectin-1 (Gal-1), a 14-kDa secreted protein that is synthesized by carcinoma cells and promotes tumor immune evasion, angiogenesis, and metastasis. Interestingly, we found that localization of Gal-1 on the surface of cells is dependent on the presence of SUSD2. Various phenotype assays indicate that SUSD2 increases the invasion of breast cancer cells and contributes to a potential immune evasion mechanism through induction of apoptosis of Jurkat T cells. Using a syngeneic mouse model, we observed accelerated tumor formation and decreased survival in mice with tumors expressing Susd2. We found significantly fewer CD4 tumor infiltrating lymphocytes in mice with tumors expressing Susd2. Together, our findings provide evidence that SUSD2 may represent a promising therapeutic target for breast cancer.",
author = "Watson, {Allison P.} and Evans, {Rick L.} and Egland, {Kristi A.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1158/1541-7786.MCR-12-0501-T",
language = "English (US)",
volume = "11",
pages = "74--85",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

TY - JOUR

T1 - Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis

AU - Watson, Allison P.

AU - Evans, Rick L.

AU - Egland, Kristi A.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Routinely used therapies are not adequate to treat the heterogeneity of breast cancer, and consequently, more therapeutic targets are desperately needed. To identify novel targets, we generated a breast cancer cDNA library enriched for genes that encode membrane and secreted proteins. From this library we identified SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein containing a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies describe the mouse homolog, Susd2, but there are no studies on the human gene associated with breast cancer. Immunohistochemical analysis of human breast tissues showed weak or no expression of SUSD2 in normal epithelial cells, with the endothelial lining of vessels staining positive for SUSD2. However, staining was observed in pathologic breast lesions and in lobular and ductal carcinomas. SUSD2 interacts with galectin-1 (Gal-1), a 14-kDa secreted protein that is synthesized by carcinoma cells and promotes tumor immune evasion, angiogenesis, and metastasis. Interestingly, we found that localization of Gal-1 on the surface of cells is dependent on the presence of SUSD2. Various phenotype assays indicate that SUSD2 increases the invasion of breast cancer cells and contributes to a potential immune evasion mechanism through induction of apoptosis of Jurkat T cells. Using a syngeneic mouse model, we observed accelerated tumor formation and decreased survival in mice with tumors expressing Susd2. We found significantly fewer CD4 tumor infiltrating lymphocytes in mice with tumors expressing Susd2. Together, our findings provide evidence that SUSD2 may represent a promising therapeutic target for breast cancer.

AB - Routinely used therapies are not adequate to treat the heterogeneity of breast cancer, and consequently, more therapeutic targets are desperately needed. To identify novel targets, we generated a breast cancer cDNA library enriched for genes that encode membrane and secreted proteins. From this library we identified SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein containing a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies describe the mouse homolog, Susd2, but there are no studies on the human gene associated with breast cancer. Immunohistochemical analysis of human breast tissues showed weak or no expression of SUSD2 in normal epithelial cells, with the endothelial lining of vessels staining positive for SUSD2. However, staining was observed in pathologic breast lesions and in lobular and ductal carcinomas. SUSD2 interacts with galectin-1 (Gal-1), a 14-kDa secreted protein that is synthesized by carcinoma cells and promotes tumor immune evasion, angiogenesis, and metastasis. Interestingly, we found that localization of Gal-1 on the surface of cells is dependent on the presence of SUSD2. Various phenotype assays indicate that SUSD2 increases the invasion of breast cancer cells and contributes to a potential immune evasion mechanism through induction of apoptosis of Jurkat T cells. Using a syngeneic mouse model, we observed accelerated tumor formation and decreased survival in mice with tumors expressing Susd2. We found significantly fewer CD4 tumor infiltrating lymphocytes in mice with tumors expressing Susd2. Together, our findings provide evidence that SUSD2 may represent a promising therapeutic target for breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=84873026663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873026663&partnerID=8YFLogxK

U2 - 10.1158/1541-7786.MCR-12-0501-T

DO - 10.1158/1541-7786.MCR-12-0501-T

M3 - Article

VL - 11

SP - 74

EP - 85

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 1

ER -