BACKGROUND: More than 70% of muscle invasive bladder cancers (MIBC) express the cell-surface antigen sialyl-Tn (sTn) that promotes motility and invasive potential of tumor cells. Effective drug testing models to optimize therapy against these tumors are warranted. MATERIALS AND METHODS: Fragments of sTn-positive MIBC were subcutaneously engrafted into nude mice and expanded until the third passage. Histology and immunoexpression of tumor markers (p53, p63, Ki-67, CK20, sTn) were studied in order to evaluate tumor phenotype maintenance. RESULTS: Tumor take rate was low in the first passage (1/9) but increased and became consistent, therefore suitable for drug testing, in the third passage (13/13). Histology and immunoexpression patterns were similar between primary tumors and xenografts. However, p53 and ki-67 levels increased with passages suggesting a selection of more proliferative clones. STn expression, even though decreased, was preserved in xenografts. CONCLUSION: We describe the first patient-derived sTn-positive xenograft model to be used for drug testing and identification of prognostic biomarkers.
BACKGROUND: More than 70% of muscle invasive bladder cancers (MIBC) express the cell-surface antigen sialyl-Tn (sTn) that promotes motility and invasive potential of tumor cells. Effective drug testing models to optimize therapy against these tumors are warranted. MATERIALS AND METHODS: Fragments of sTn-positive MIBC were subcutaneously engrafted into nude mice and expanded until the third passage. Histology and immunoexpression of tumor markers (p53, p63, Ki-67, CK20, sTn) were studied in order to evaluate tumor phenotype maintenance. RESULTS:Tumor take rate was low in the first passage (1/9) but increased and became consistent, therefore suitable for drug testing, in the third passage (13/13). Histology and immunoexpression patterns were similar between primary tumors and xenografts. However, p53 and ki-67 levels increased with passages suggesting a selection of more proliferative clones. STn expression, even though decreased, was preserved in xenografts. CONCLUSION: We describe the first patient-derived sTn-positive xenograft model to be used for drug testing and identification of prognostic biomarkers.
Entities:
Keywords:
Human xenografts; animal models; drug testing; glycosylation; sialyl-Tn; urothelial cancer
Authors: Lei Wei; Sreenivasulu Chintala; Eric Ciamporcero; Swathi Ramakrishnan; May Elbanna; Jianmin Wang; Qiang Hu; Sean T Glenn; Mitsuko Murakami; Lu Liu; Eduardo Cortes Gomez; Yuchen Sun; Jacob Conroy; Kiersten Marie Miles; Kullappan Malathi; Sudha Ramaiah; Anand Anbarasu; Anna Woloszynska-Read; Candace S Johnson; Jeffrey Conroy; Song Liu; Carl D Morrison; Roberto Pili Journal: Oncotarget Date: 2016-11-22
Authors: Céu Costa; Sofia Pereira; Luís Lima; Andreia Peixoto; Elisabete Fernandes; Diogo Neves; Manuel Neves; Cristiana Gaiteiro; Ana Tavares; Rui M Gil da Costa; Ricardo Cruz; Teresina Amaro; Paula A Oliveira; José Alexandre Ferreira; Lúcio L Santos Journal: PLoS One Date: 2015-11-16 Impact factor: 3.240
Authors: Andreia Peixoto; Elisabete Fernandes; Cristiana Gaiteiro; Luís Lima; Rita Azevedo; Janine Soares; Sofia Cotton; Beatriz Parreira; Manuel Neves; Teresina Amaro; Ana Tavares; Filipe Teixeira; Carlos Palmeira; Maria Rangel; André M N Silva; Celso A Reis; Lúcio Lara Santos; Maria José Oliveira; José Alexandre Ferreira Journal: Oncotarget Date: 2016-09-27