Abstract
AimTo develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule.MethodsCervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the renal capsule of immunocompromised NOD/SCID/gamma mice. Resulting tumours were harvested and portions serially transplanted into new recipient mice for up to three in vivo passages. Parent and xenograft tumours were examined by immunohistochemistry for p16INK41, HPV, and CD-45. Single cell suspensions of mixed mouse and human, or human only cell populations were also transplanted.ResultsThe overall engraftment rate for the primary cervical cancer PDX model was 71.4 ±12.5% (n = 14). Tumours maintained morphological, histoarchitecture and immunohistochemical features of the parent tumour, and demonstrated invasiveness into local tissues. Single cell suspensions did not produce tumour growth in this model. Mean length of time (32.4 +/- 3.5 weeks) for the transplanted tissue to generate a tumour in the animal was similar between successive transplantations. Three of four xenografted cervical dysplasia tissues generated microscopic cystic structures resembling dysplastic cervical tissue. Normal cervical tissue (4 of 5 xenografted) also developed microscopic cervical tissue grafts.ConclusionThe subrenal capsule can be used for a PDX model of human cervical cancer with a good engraftment rate and the ability to model in vivo characteristics of cervical cancer. For the first time we have demonstrated that cervical dysplasia and normal cervical tissue generated microscopic tissues in a PDX model.
Highlights
Cervical cancer is a leading cause of morbidity and mortality for women worldwide
The subrenal capsule can be used for a patient derived xenograft (PDX) model of human cervical cancer with a good engraftment rate and the ability to model in vivo characteristics of cervical cancer
For the first time we have demonstrated that cervical dysplasia and normal cervical tissue generated microscopic tissues in a PDX model
Summary
Cervical cancer is a leading cause of morbidity and mortality for women worldwide. It is the fourth most common cancer for women globally, with approximately 84% of cases occurring in the developing world [1]. Detection and prevention of cervical cancer is based on the existence of a clear premalignant state, cervical dysplasia, and that the Human Papilloma Virus (HPV) is essential to cervical cancer development [2]. Radiotherapy is the mainstay of treatment for women with advanced disease [3,4], and attempts to find new treatments have been unsuccessful [5]. There is a need for models to further study cervical dysplasia and cancer, and test new therapies
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