Abstract
In order to develop a practical model of breast cancer, with in vitro and syngeneic, immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as “NDL UCD ”. The cell line is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. NDL UCD tumors in FVB/N mice exhibit high expression of ErbB2 and ErbB3 and signaling molecules downstream of ErbB2. The syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, detected and characterized using histology, immunophenotyping, and gene expression. NDL UCD cells also express PD-L1 in vivo and in vitro, and in vivo transplants are reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. This new NDL UCD cell line model is a practical alternative to the more commonly used 4T1 cells, and our previously described FVB/N-Tg(MMTV-PyVT)634Mul derived Met-1 fvb2 and FVB/NTg(MMTV-PyVT Y315F/Y322F ) derived DB-7 fvb2 cell lines. The NDL UCD cells have, so far, remained genetically and phenotypically stable over many generations, with consistent and reproducible results in immune intact preclinical cohorts.
| Original language | English (US) |
|---|---|
| Journal | Journal of Mammary Gland Biology and Neoplasia |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Breast cancer
- Erbb2
- Immunotherapy
- Mouse model
- PD-L1
- Syngeneic
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials. / Pénzváltó, Zsófia; Chen, Jane Qian; Tepper, Clifford G; Davis, Ryan R.; Silvestrini, Matthew T.; Umeh-Garcia, Maxine; Sweeney, Colleen A; Borowsky, Alexander D.
In: Journal of Mammary Gland Biology and Neoplasia, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials
AU - Pénzváltó, Zsófia
AU - Chen, Jane Qian
AU - Tepper, Clifford G
AU - Davis, Ryan R.
AU - Silvestrini, Matthew T.
AU - Umeh-Garcia, Maxine
AU - Sweeney, Colleen A
AU - Borowsky, Alexander D
PY - 2019/1/1
Y1 - 2019/1/1
N2 - In order to develop a practical model of breast cancer, with in vitro and syngeneic, immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as “NDL UCD ”. The cell line is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. NDL UCD tumors in FVB/N mice exhibit high expression of ErbB2 and ErbB3 and signaling molecules downstream of ErbB2. The syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, detected and characterized using histology, immunophenotyping, and gene expression. NDL UCD cells also express PD-L1 in vivo and in vitro, and in vivo transplants are reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. This new NDL UCD cell line model is a practical alternative to the more commonly used 4T1 cells, and our previously described FVB/N-Tg(MMTV-PyVT)634Mul derived Met-1 fvb2 and FVB/NTg(MMTV-PyVT Y315F/Y322F ) derived DB-7 fvb2 cell lines. The NDL UCD cells have, so far, remained genetically and phenotypically stable over many generations, with consistent and reproducible results in immune intact preclinical cohorts.
AB - In order to develop a practical model of breast cancer, with in vitro and syngeneic, immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as “NDL UCD ”. The cell line is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. NDL UCD tumors in FVB/N mice exhibit high expression of ErbB2 and ErbB3 and signaling molecules downstream of ErbB2. The syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, detected and characterized using histology, immunophenotyping, and gene expression. NDL UCD cells also express PD-L1 in vivo and in vitro, and in vivo transplants are reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. This new NDL UCD cell line model is a practical alternative to the more commonly used 4T1 cells, and our previously described FVB/N-Tg(MMTV-PyVT)634Mul derived Met-1 fvb2 and FVB/NTg(MMTV-PyVT Y315F/Y322F ) derived DB-7 fvb2 cell lines. The NDL UCD cells have, so far, remained genetically and phenotypically stable over many generations, with consistent and reproducible results in immune intact preclinical cohorts.
KW - Breast cancer
KW - Erbb2
KW - Immunotherapy
KW - Mouse model
KW - PD-L1
KW - Syngeneic
UR - http://www.scopus.com/inward/record.url?scp=85062640375&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062640375&partnerID=8YFLogxK
U2 - 10.1007/s10911-019-09425-3
DO - 10.1007/s10911-019-09425-3
M3 - Article
C2 - 30810966
AN - SCOPUS:85062640375
JO - Journal of Mammary Gland Biology and Neoplasia
JF - Journal of Mammary Gland Biology and Neoplasia
SN - 1083-3021
ER -