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Erschienen in: Clinical & Experimental Metastasis 2/2020

14.01.2020 | Technical Note

The utility of the “Glowing Head” mouse for breast cancer metastasis research

verfasst von: Mohammad A. Alzubi, David C. Boyd, J. Chuck Harrell

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 2/2020

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Abstract

The expression of cellular reporters to label cancer cells, such as green fluorescent protein (GFP) and luciferase, can stimulate immune responses and effect tumor growth. Recently, a mouse model that expresses GFP and luciferase in the anterior pituitary gland was generated to tolerize mice to these proteins; the “Glowing Head” mouse. Mice were obtained from a commercial vendor, bred, and then used for tumor growth and metastasis studies. The transgene expression of luciferase was assessed within tumor-naïve mice as well as mice with mammary tumors or metastases. Tumor-free mice with white fur, compared to black fur, allowed for stronger luciferase transgene expression to be observed in the pituitary, sternum, and femur. Growth of four different luciferase-expressing mouse cancer cell lines readily occurred in the mammary gland. Though sternum expression of the luciferase transgene occurred in cancer-free mice, growth or death of luciferase positive cancer cells in the lung could be observed. Liver metastases seeded by portal vein injections of luciferase positive cancer cell lines were completely distinct from luciferase transgene expression. Though lung and brain metastasis studies have limitations, the Glowing Head mouse can be useful to inhibit immune system rejection of luciferase or GFP expressing cancer cells. This mouse model is most beneficial for studies of mammary tumors and liver metastases.
Literatur
2.
Zurück zum Zitat Hart IR, Fidler IJ (1980) Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res 40(7):2281–2287PubMed Hart IR, Fidler IJ (1980) Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res 40(7):2281–2287PubMed
3.
Zurück zum Zitat Fidler IJ (1970) Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125 I-5-iodo-2'-deoxyuridine. J Natl Cancer Inst 45(4):773–782PubMed Fidler IJ (1970) Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125 I-5-iodo-2'-deoxyuridine. J Natl Cancer Inst 45(4):773–782PubMed
4.
Zurück zum Zitat Brunner N, Thompson EW, Spang-Thomsen M, Rygaard J, Dano K, Zwiebel JA (1992) lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis. Eur J Cancer 28A(12):1989–1995CrossRef Brunner N, Thompson EW, Spang-Thomsen M, Rygaard J, Dano K, Zwiebel JA (1992) lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis. Eur J Cancer 28A(12):1989–1995CrossRef
5.
Zurück zum Zitat Chishima T, Yang M, Miyagi Y, Li L, Tan Y, Baranov E, Shimada H, Moossa AR, Penman S, Hoffman RM (1997) Governing step of metastasis visualized in vitro. Proc Natl Acad Sci USA 94(21):11573–11576CrossRef Chishima T, Yang M, Miyagi Y, Li L, Tan Y, Baranov E, Shimada H, Moossa AR, Penman S, Hoffman RM (1997) Governing step of metastasis visualized in vitro. Proc Natl Acad Sci USA 94(21):11573–11576CrossRef
6.
Zurück zum Zitat Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5(10):796–806CrossRef Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5(10):796–806CrossRef
7.
Zurück zum Zitat Yang M, Baranov E, Jiang P, Sun FX, Li XM, Li L, Hasegawa S, Bouvet M, Al-Tuwaijri M, Chishima T, Shimada H, Moossa AR, Penman S, Hoffman RM (2000) Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci USA 97(3):1206–1211CrossRef Yang M, Baranov E, Jiang P, Sun FX, Li XM, Li L, Hasegawa S, Bouvet M, Al-Tuwaijri M, Chishima T, Shimada H, Moossa AR, Penman S, Hoffman RM (2000) Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci USA 97(3):1206–1211CrossRef
8.
Zurück zum Zitat Bourett TM, Sweigard JA, Czymmek KJ, Carroll A, Howard RJ (2002) Reef coral fluorescent proteins for visualizing fungal pathogens. Fungal Genet Biol 37(3):211–220CrossRef Bourett TM, Sweigard JA, Czymmek KJ, Carroll A, Howard RJ (2002) Reef coral fluorescent proteins for visualizing fungal pathogens. Fungal Genet Biol 37(3):211–220CrossRef
9.
Zurück zum Zitat Harrell JC, Dye WW, Allred DC, Jedlicka P, Spoelstra NS, Sartorius CA, Horwitz KB (2006) Estrogen receptor positive breast cancer metastasis: altered hormonal sensitivity and tumor aggressiveness in lymphatic vessels and lymph nodes. Cancer Res 66(18):9308–9315CrossRef Harrell JC, Dye WW, Allred DC, Jedlicka P, Spoelstra NS, Sartorius CA, Horwitz KB (2006) Estrogen receptor positive breast cancer metastasis: altered hormonal sensitivity and tumor aggressiveness in lymphatic vessels and lymph nodes. Cancer Res 66(18):9308–9315CrossRef
10.
Zurück zum Zitat Harrell JC, Dye WW, Harvell DM, Pinto M, Jedlicka P, Sartorius CA, Horwitz KB (2007) Estrogen insensitivity in a model of estrogen receptor positive breast cancer lymph node metastasis. Cancer Res 67(21):10582–10591CrossRef Harrell JC, Dye WW, Harvell DM, Pinto M, Jedlicka P, Sartorius CA, Horwitz KB (2007) Estrogen insensitivity in a model of estrogen receptor positive breast cancer lymph node metastasis. Cancer Res 67(21):10582–10591CrossRef
11.
Zurück zum Zitat Spillman MA, Manning NG, Dye WW, Sartorius CA, Post MD, Harrell JC, Jacobsen BM, Horwitz KB (2010) Tissue-specific pathways for estrogen regulation of ovarian cancer growth and metastasis. Cancer Res 70(21):8927–8936CrossRef Spillman MA, Manning NG, Dye WW, Sartorius CA, Post MD, Harrell JC, Jacobsen BM, Horwitz KB (2010) Tissue-specific pathways for estrogen regulation of ovarian cancer growth and metastasis. Cancer Res 70(21):8927–8936CrossRef
12.
Zurück zum Zitat Sadikot RT, Blackwell TS (2005) Bioluminescence imaging. Proc Am Thorac Soc 2(6):537–540, 511–512 Sadikot RT, Blackwell TS (2005) Bioluminescence imaging. Proc Am Thorac Soc 2(6):537–540, 511–512
13.
Zurück zum Zitat Flanagan SP (1966) 'Nude', a new hairless gene with pleiotropic effects in the mouse. Genet Res 8(3):295–309CrossRef Flanagan SP (1966) 'Nude', a new hairless gene with pleiotropic effects in the mouse. Genet Res 8(3):295–309CrossRef
14.
Zurück zum Zitat Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, Kotb M, Gillies SD, King M, Mangada J, Greiner DL, Handgretinger R (2005) Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174(10):6477–6489CrossRef Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, Kotb M, Gillies SD, King M, Mangada J, Greiner DL, Handgretinger R (2005) Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174(10):6477–6489CrossRef
15.
Zurück zum Zitat Alzubi MA, Sohal SS, Sriram M, Turner TH, Zot P, Idowu M, Harrell JC (2019) Quantitative assessment of breast cancer liver metastasis expansion with patient-derived xenografts. Clin Exp Metastasis 36(3):257–269CrossRef Alzubi MA, Sohal SS, Sriram M, Turner TH, Zot P, Idowu M, Harrell JC (2019) Quantitative assessment of breast cancer liver metastasis expansion with patient-derived xenografts. Clin Exp Metastasis 36(3):257–269CrossRef
16.
Zurück zum Zitat Alzubi MA, Turner TH, Olex AL, Sohal SS, Tobin NP, Recio SG, Bergh J, Hatschek T, Parker JS, Sartorius CA, Perou CM, Dozmorov MG, Harrell JC (2019) Separation of breast cancer and organ microenvironment transcriptomes in metastases. Breast Cancer Res 21(1):36CrossRef Alzubi MA, Turner TH, Olex AL, Sohal SS, Tobin NP, Recio SG, Bergh J, Hatschek T, Parker JS, Sartorius CA, Perou CM, Dozmorov MG, Harrell JC (2019) Separation of breast cancer and organ microenvironment transcriptomes in metastases. Breast Cancer Res 21(1):36CrossRef
17.
Zurück zum Zitat Murray GF, Turner TH, Leslie KA, Alzubi MA, Guest D, Sohal SS, Teitell MA, Harrell JC, Reed J (2018) Live cell mass accumulation measurement non-invasively predicts carboplatin sensitivity in triple-negative breast cancer patient-derived xenografts. ACS Omega 3(12):17687–17692CrossRef Murray GF, Turner TH, Leslie KA, Alzubi MA, Guest D, Sohal SS, Teitell MA, Harrell JC, Reed J (2018) Live cell mass accumulation measurement non-invasively predicts carboplatin sensitivity in triple-negative breast cancer patient-derived xenografts. ACS Omega 3(12):17687–17692CrossRef
18.
Zurück zum Zitat Turner TH, Alzubi MA, Sohal SS, Olex AL, Dozmorov MG, Harrell JC (2018) Characterizing the efficacy of cancer therapeutics in patient-derived xenograft models of metastatic breast cancer. Breast Cancer Res Treat 170(2):221–234CrossRef Turner TH, Alzubi MA, Sohal SS, Olex AL, Dozmorov MG, Harrell JC (2018) Characterizing the efficacy of cancer therapeutics in patient-derived xenograft models of metastatic breast cancer. Breast Cancer Res Treat 170(2):221–234CrossRef
19.
Zurück zum Zitat Baklaushev VP, Kilpelainen A, Petkov S, Abakumov MA, Grinenko NF, Yusubalieva GM, Latanova AA, Gubskiy IL, Zabozlaev FG, Starodubova ES, Abakumova TO, Isaguliants MG, Chekhonin VP (2017) Luciferase expression allows bioluminescence imaging but imposes limitations on the orthotopic mouse (4T1) model of breast cancer. Sci Rep 7(1):7715CrossRef Baklaushev VP, Kilpelainen A, Petkov S, Abakumov MA, Grinenko NF, Yusubalieva GM, Latanova AA, Gubskiy IL, Zabozlaev FG, Starodubova ES, Abakumova TO, Isaguliants MG, Chekhonin VP (2017) Luciferase expression allows bioluminescence imaging but imposes limitations on the orthotopic mouse (4T1) model of breast cancer. Sci Rep 7(1):7715CrossRef
20.
Zurück zum Zitat Steinbauer M, Guba M, Cernaianu G, Kohl G, Cetto M, Kunz-Schughart LA, Geissler EK, Falk W, Jauch KW (2003) GFP-transfected tumor cells are useful in examining early metastasis in vivo, but immune reaction precludes long-term tumor development studies in immunocompetent mice. Clin Exp Metastasis 20(2):135–141CrossRef Steinbauer M, Guba M, Cernaianu G, Kohl G, Cetto M, Kunz-Schughart LA, Geissler EK, Falk W, Jauch KW (2003) GFP-transfected tumor cells are useful in examining early metastasis in vivo, but immune reaction precludes long-term tumor development studies in immunocompetent mice. Clin Exp Metastasis 20(2):135–141CrossRef
21.
Zurück zum Zitat Stripecke R, Carmen Villacres M, Skelton D, Satake N, Halene S, Kohn D (1999) Immune response to green fluorescent protein: implications for gene therapy. Gene Ther 6(7):1305–1312CrossRef Stripecke R, Carmen Villacres M, Skelton D, Satake N, Halene S, Kohn D (1999) Immune response to green fluorescent protein: implications for gene therapy. Gene Ther 6(7):1305–1312CrossRef
22.
Zurück zum Zitat Andersson G, Denaro M, Johnson K, Morgan P, Sullivan A, Houser S, Patience C, White-Scharf ME, Down JD (2003) Engraftment of retroviral EGFP-transduced bone marrow in mice prevents rejection of EGFP-transgenic skin grafts. Mol Ther 8(3):385–391CrossRef Andersson G, Denaro M, Johnson K, Morgan P, Sullivan A, Houser S, Patience C, White-Scharf ME, Down JD (2003) Engraftment of retroviral EGFP-transduced bone marrow in mice prevents rejection of EGFP-transgenic skin grafts. Mol Ther 8(3):385–391CrossRef
23.
Zurück zum Zitat Day CP, Carter J, Weaver Ohler Z, Bonomi C, El Meskini R, Martin P, Graff Cherry C, Feigenbaum L, Tuting T, Van Dyke T, Hollingshead M, Merlino G (2014) "Glowing head" mice: a genetic tool enabling reliable preclinical image-based evaluation of cancers in immunocompetent allografts. PLoS ONE 9(11):e109956CrossRef Day CP, Carter J, Weaver Ohler Z, Bonomi C, El Meskini R, Martin P, Graff Cherry C, Feigenbaum L, Tuting T, Van Dyke T, Hollingshead M, Merlino G (2014) "Glowing head" mice: a genetic tool enabling reliable preclinical image-based evaluation of cancers in immunocompetent allografts. PLoS ONE 9(11):e109956CrossRef
24.
Zurück zum Zitat Dongre A, Rashidian M, Reinhardt F, Bagnato A, Keckesova Z, Ploegh HL, Weinberg RA (2017) Epithelial-to-mesenchymal transition contributes to immunosuppression in breast carcinomas. Cancer Res 77(15):3982–3989CrossRef Dongre A, Rashidian M, Reinhardt F, Bagnato A, Keckesova Z, Ploegh HL, Weinberg RA (2017) Epithelial-to-mesenchymal transition contributes to immunosuppression in breast carcinomas. Cancer Res 77(15):3982–3989CrossRef
25.
Zurück zum Zitat Gibby K, You WK, Kadoya K, Helgadottir H, Young LJ, Ellies LG, Chang Y, Cardiff RD, Stallcup WB (2012) Early vascular deficits are correlated with delayed mammary tumorigenesis in the MMTV-PyMT transgenic mouse following genetic ablation of the NG2 proteoglycan. Breast Cancer Res 14(2):R67CrossRef Gibby K, You WK, Kadoya K, Helgadottir H, Young LJ, Ellies LG, Chang Y, Cardiff RD, Stallcup WB (2012) Early vascular deficits are correlated with delayed mammary tumorigenesis in the MMTV-PyMT transgenic mouse following genetic ablation of the NG2 proteoglycan. Breast Cancer Res 14(2):R67CrossRef
26.
Zurück zum Zitat Dunham LJ, Stewart HL (1953) A survey of transplantable and transmissible animal tumors. J Natl Cancer Inst 13(5):1299–1377PubMed Dunham LJ, Stewart HL (1953) A survey of transplantable and transmissible animal tumors. J Natl Cancer Inst 13(5):1299–1377PubMed
27.
Zurück zum Zitat Carlson P, Dasgupta A, Grzelak CA, Kim J, Barrett A, Coleman IM, Shor RE, Goddard ET, Dai J, Schweitzer EM, Lim AR, Crist SB, Cheresh DA, Nelson PS, Hansen KC, Ghajar CM (2019) Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy. Nat Cell Biol 21(2):238–250CrossRef Carlson P, Dasgupta A, Grzelak CA, Kim J, Barrett A, Coleman IM, Shor RE, Goddard ET, Dai J, Schweitzer EM, Lim AR, Crist SB, Cheresh DA, Nelson PS, Hansen KC, Ghajar CM (2019) Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy. Nat Cell Biol 21(2):238–250CrossRef
Metadaten
Titel
The utility of the “Glowing Head” mouse for breast cancer metastasis research
verfasst von
Mohammad A. Alzubi
David C. Boyd
J. Chuck Harrell
Publikationsdatum
14.01.2020
Verlag
Springer Netherlands
Erschienen in
Clinical & Experimental Metastasis / Ausgabe 2/2020
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-020-10020-8

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