An improved method to study NK-independent mechanisms of MTLn3 breast cancer lung metastasis

Nimwegen, Maroesja J. van; Verkoeijen, Saertje; Kuppen, Peter J. K.; Velthuis, Jurjen H.L.; Water, Bob van de

doi:10.1007/s10585-007-9075-9

Cited by 5 publications

(6 citation statements)

References 23 publications

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“…Rat models of MM have been successfully used for decades to decipher the different stages of MM molecular pathogenesis [19]. The immunocompetent inbred F344 rat strain F344 is a good experimental base for designing syngeneic orthotopic tumor models, which are preferable when considering tumor versus immune cell interactions [17,20], and when evaluating the therapeutic efficacy of new drugs [21]. Moreover, this type of experimental model allows MRI monitoring [22].…”

Section: Introductionmentioning

confidence: 99%

S100A4 Is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma

Nader

Guillon

Petit

et al. 2020

Cancers

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Recent findings suggest that S100A4, a protein involved in communication between stromal cells and cancer cells, could be more involved than previously expected in cancer invasiveness. To investigate its cumulative value in the multistep process of the pathogenesis of malignant mesothelioma (MM), SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra), an advanced and robust technique of quantitative proteomics, was used to analyze a collection of 26 preneoplastic and neoplastic rat mesothelial cell lines and models of MM with increasing invasiveness. Secondly, proteomic and histological analyses were conducted on formalin-fixed paraffin-embedded sections of liver metastases vs. primary tumor, and spleen from tumor-bearing rats vs. controls in the most invasive MM model. We found that S100A4, along with 12 other biomarkers, differentiated neoplastic from preneoplastic mesothelial cell lines, and invasive vs. non-invasive tumor cells in vitro, and MM tumors in vivo. Additionally, S100A4 was the only protein differentiating preneoplastic mesothelial cell lines with sarcomatoid vs. epithelioid morphology in relation to EMT (epithelial-to-mesenchymal transition). Finally, S100A4 was the most significantly increased biomarker in liver metastases vs. primary tumor, and in the spleen colonized by MM cells. Overall, we showed that S100A4 was the only protein that showed increased abundance in all situations, highlighting its crucial role in all stages of MM pathogenesis.

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Section: Introductionmentioning

confidence: 99%

S100A4 Is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma

Nader

Guillon

Petit

et al. 2020

Cancers

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“…Previously, we demonstrated a negative role of NK immune cells in lung metastasis formation in Fischer 344 rats [ 27 ]. We analyzed several immune deficient mouse models for their capacity to support orthotopic breast cancer metastasis formation.…”

Section: Resultsmentioning

confidence: 99%

“…In this study, we have shown that the presence of remaining innate immune cells, including NK cells, in the nude and SCID mouse does not affect the growth of the primary tumor but inhibits the formation of lung metastases [ 6 , 17 , 27 , 38 ]. Indeed, we have found that the Rag2 −/− γc −/− mouse which lacks NK cells is an excellent recipient animal model to study breast tumor formation and progression when using MTLn3 overexpressing ErbB1 cells or 4T1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, we showed previously that the MTLn3 cells are killed by the circulating NK-cells in Fischer 344 rats, thus preventing efficient lung metastasis formation. Although pretreatment with NK-depleting antibodies allowed experimental lung metastasis formation in this model [ 26 , 27 ], continuous NK depleting antibody injection is an undesirable requirement for a breast/tumor metastasis model. To study breast tumor progression and metastasis formation using MTLn3 cells expressing the EGF receptor, an appropriate animal model with a compromised innate and adaptive immune system was still required.…”

Section: Introductionmentioning

confidence: 99%

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An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2−/− γc−/− mouse

Dévédec

Roosmalen

Maria

et al. 2009

Clin Exp Metastasis

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The occurrence of metastases is a critical determinant of the prognosis for breast cancer patients. Effective treatment of breast cancer metastases is hampered by a poor understanding of the mechanisms involved in the formation of these secondary tumor deposits. To study the processes of metastasis, valid in vivo tumor metastasis models are required. Here, we show that increased expression of the EGF receptor in the MTLn3 rat mammary tumor cell-line is essential for efficient lung metastasis formation in the Rag mouse model. EGFR expression resulted in delayed orthotopic tumor growth but at the same time strongly enhanced intravasation and lung metastasis. Previously, we demonstrated the critical role of NK cells in a lung metastasis model using MTLn3 cells in syngenic F344 rats. However, this model is incompatible with human EGFR. Using the highly metastatic EGFRoverexpressing MTLn3 cell-line, we report that only Rag2 -/-cc -/-mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland. In contrast, in nude and SCID mice, the remaining innate immune cells reduce MTLn3 lung metastasis formation. Furthermore, we confirm this finding with the orthotopic transplantation of the 4T1 mouse mammary tumor cell-line. Thus, we have established an improved in vivo model using a Rag2 -/-cc -/-mouse strain together with MTLn3 cells that have increased levels of the EGF receptor, which enables us to study EGFR-dependent tumor cell autonomous mechanisms underlying lung metastasis formation. This improved model can be used for drug target validation and development of new therapeutic strategies against breast cancer metastasis formation.

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“…Gene-modified DC coculture with T-lymphocyte will elicit specific immune responses. SLC and IL-2 have strong antitumor effects, respectively, and the SLC antitumor study was mainly for liver, prostate, and gastric cancers (22,23), while the IL-2 study was for lung, renal, prostate, and bladder cancers (24,25). Further, coculture of DC, TC, and bladder tumor cells will enhance their talk, as results revealed that TC-DC has strong toxicity to bladder tumor cells and induced bladder tumor cell apoptosis.…”

Section: Discussionmentioning

confidence: 97%

Dendritic Cell Transfected with Secondary Lymphoid-Tissue Chemokine and/or Interleukin-2 Gene-Enhanced Cytotoxicity of T-Lymphocyte in Human Bladder Tumor Cell SIn Vitro

Wang

Tian

et al. 2009

Cancer Investigation

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An improved method to study NK-independent mechanisms of MTLn3 breast cancer lung metastasis

Abstract: To study the tumor cell autonomous processes of metastasis, an in vivo tumor metastasis model is required that excludes the involvement of the innate immune system. For this purpose we used the established syngeneic

Cited by 5 publications

References 23 publications

S100A4 Is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma

S100A4 Is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma

An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2−/− γc−/− mouse

Dendritic Cell Transfected with Secondary Lymphoid-Tissue Chemokine and/or Interleukin-2 Gene-Enhanced Cytotoxicity of T-Lymphocyte in Human Bladder Tumor Cell SIn Vitro

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