Establishment of Human Patient-Derived Endometrial Cancer Xenografts in NOD scid Gamma Mice for the Study of Invasion and Metastasis

Abstract

ObjectiveMost endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.MethodsEndometrial tumor tissue fragments (1.5 mm×1.5 mm) from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6–8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.ResultsFour cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.ConclusionEndometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.

CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors

“…Endometrioid TOV112D ovarian cancer cell line was cultured in a 1:1 mixture of MCDB 105 medium and Medium 199, supplemented with 15% HI-FBS. Patient-derived primary endometrioid endometrial cancer xenograft (PDX) EEC-4 was a gift from J.J.Kim’s laboratory and maintained in RPMI 1640 with 10% HI-FBS ( Unno et al, 2014 ). Cisplatin-resistant primary endometrial cancer cell line HEC1a was cultured in modified McCoy’s 5a medium.…”

Patient-Derived Xenograft Models for Endometrial Cancer Research

“…On the other hand, Unno et al [ 34 ] established a xenograft model by transplanting fragments of four different EC histologies, from patients undergoing surgery, into the renal capsule of NSG mice. Following this approach, the authors reported that tumour xenografts retain characteristics of the original tumour and display features that are unique to endometrioid EC or non-endometrioid EC.…”

“…Following this approach, the authors reported that tumour xenografts retain characteristics of the original tumour and display features that are unique to endometrioid EC or non-endometrioid EC. In addition, they showed that each model has a different invasive and metastatic capacity according to its histology as well as a distinct dependence on β-estradiol [ 34 ]. Despite the technical difficulties presented by this type of approach, a renal capsule xenograft model is suitable for studying aggressive EC since tumour cells are in an environment susceptible to invasion and metastasis.…”

CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors

“…Endometrioid TOV112D ovarian cancer cell line was cultured in a 1:1 mixture of MCDB 105 medium and Medium 199, supplemented with 15% HI-FBS. Patientderived primary endometrioid endometrial cancer xenograft (PDX) EEC-4 was a kind gift from Dr. Kim's laboratory and maintained in RPMI 1640 with 10% HI-FBS (Unno K, 2014). Cisplatin-resistant primary endometrial cancer cell line HEC1a was cultured in modified McCoy's 5a medium.…”