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Mejia Cordova, Mariela
Publications (4 of 4) Show all publications
He, Q., Li, X., Singh, K., Luo, Z., Meija-Cordova, M., Jamalpour, M., . . . Welsh, M. (2019). The Cdh5-CreERT2 transgene causes conditional Shb gene deletion in hematopoietic cells with consequences for immune cell responses to tumors. Scientific Reports, 9, Article ID 7548.
Open this publication in new window or tab >>The Cdh5-CreERT2 transgene causes conditional Shb gene deletion in hematopoietic cells with consequences for immune cell responses to tumors
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7548Article in journal (Refereed) Published
Abstract [en]

The tamoxifen-responsive conditional Cdh5-CreERT2 is commonly used for endothelial cell specific conditional deletion of loxP-flanked gene sequences. To address the role of endothelial cell Shb gene for B16F10 melanoma immune responses, tamoxifen-injected Cdh5-CreERT2/WT and Cdh5-CreERT2/Shbflox/flox mice received subcutaneous tumor cell injections. We observed a decrease of tumor myeloid cell Shb mRNA in the tamoxifen treated Cdh5-CreERT2/Shbflox/flox mice, which was not present when the mice had undergone a preceding bone marrow transplantation using wild type bone marrow. Differences in CD4+/FoxP3+ Tregs were similarly abolished by a preceding bone marrow transplantation. In ROSA26-mTmG mice, Cdh5-CreERT2 caused detectable floxing in certain bone marrow populations and in spleen cells. Floxing in bone marrow could be detected two months after tamoxifen treatment. In the spleen, however, floxing was undetectable two months after tamoxifen treatment, suggesting that Cdh5-CreERT2 is operating in a non-renewable population of hematopoietic cells in this organ. These data suggest that conditional gene deletion in hematopoietic cells is a potential confounder in experiments attempting to assess the role of endothelial specific effects. A cautious approach to achieve an endothelial-specific phenotype would be to adopt a strategy that includes a preceding bone marrow transplantation.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-383581 (URN)10.1038/s41598-019-44039-z (DOI)000468171100043 ()31101877 (PubMedID)
Funder
Swedish Cancer Society, 180767Swedish Research Council, 2016-01085EU, FP7, Seventh Framework Programme, 312325EXODIAB - Excellence of Diabetes Research in SwedenErnfors Foundation
Available from: 2019-05-17 Created: 2019-05-17 Last updated: 2019-06-24Bibliographically approved
Li, X., Singh, K., Luo, Z., Mejia Cordova, M., Jamalpour, M., Lindahl, B., . . . Welsh, M. (2018). Pro-tumoral immune cell alterations in wild type and Shb-deficient mice in response to 4T1 breast carcinomas. OncoTarget, 9(27), 18720-18733
Open this publication in new window or tab >>Pro-tumoral immune cell alterations in wild type and Shb-deficient mice in response to 4T1 breast carcinomas
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2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 27, p. 18720-18733Article in journal (Refereed) Published
Abstract [en]

To assess mechanisms responsible for breast carcinoma metastasis, 4T1 breast carcinomas were grown orthotopically in wild type or Shb knockout mice. Tumor growth, metastasis, vascular characteristics and immune cell properties were analyzed. Absence of Shb did not affect tumor growth although it increased lung metastasis. Shb knockout mouse tumors showed decreased redness and less developed vascular plexa located at the periphery of the tumors. No difference in overall tumor vascular density, leakage or pericyte coverage was noted between the genotypes although the average vessel size was smaller in the knockout. Tumors induced an increase of CD11b+ cells in spleen, lymph node, thymus, bone marrow and blood. Numbers of Shb knockout CD11b/CD8+ cells were decreased in lymph nodes and bone marrow of tumor bearing mice. Mice with tumors had reduced numbers of CD4+ lymphocytes in blood/lymphoid organs, whereas in most of these locations the proportion of CD4+ cells co-expressing FoxP3 was increased, suggesting a relative increase in Treg cells. This finding was reinforced by increased blood interleukin-35 (IL-35) in wild type tumor bearing mice. Shb knockout blood showed in addition an increased proportion of IL-35 expressing Treg cells, supporting the notion that absence of Shb further promotes tumor evasion from immune cell recognition. This could explain the increased number of lung metastases observed under these conditions. In conclusion, 4T1 tumors alter immune cell responses that promote tumor expansion, metastasis and escape from T cell recognition in an Shb dependent manner. 

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-347019 (URN)10.18632/oncotarget.24643 (DOI)
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-04-12Bibliographically approved
Mejia Cordova, M., Soläng, C., Luo, Z., Blixt, M., Thorvaldson, L., Sandler, S. & Singh, K. (2017). Kinetics of the innate immune cell responses in experimental Type 1 Diabetes. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 303-304
Open this publication in new window or tab >>Kinetics of the innate immune cell responses in experimental Type 1 Diabetes
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 303-304Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-346961 (URN)000411865200134 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-03-23Bibliographically approved
Lundin, S., Espes, D., Luo, Z., Blixt, M., Mejia Cordova, M., Carlsson, P.-O., . . . Singh, K. (2017). Role of regulatory B cells in clinical and experimental type 1 diabetes. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 349-349
Open this publication in new window or tab >>Role of regulatory B cells in clinical and experimental type 1 diabetes
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 349-349Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-346972 (URN)000411865200233 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28Bibliographically approved
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