A patient derived xenograft model of cervical cancer and cervical dysplasia

Aim
To develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule.
Methods
Cervical 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.
Results
The 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.
Conclusion
The 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.

## 研究目的
构建基于肾被膜下（subrenal capsule）移植的宫颈癌及宫颈发育异常患者来源异种移植（patient derived xenograft, PDX）模型。

## 研究方法
纳入宫颈癌组织14例（12例鳞状细胞癌、1例腺癌、1例腺鳞癌）、7例宫颈发育异常活检组织及正常宫颈组织，将上述组织移植至免疫缺陷型NOD/SCID/γ小鼠的肾被膜下。收获移植形成的肿瘤后，将部分组织连续移植至新的受体小鼠体内，最多可完成3代体内传代。采用免疫组织化学法检测亲本肿瘤及异种移植瘤的p16INK41、人乳头瘤病毒（Human Papillomavirus, HPV）及CD-45表达水平；同时还制备了混合小鼠-人类细胞群或仅人类细胞群的单细胞悬液进行移植实验。

## 研究结果
原发性宫颈癌PDX模型的总体植入率为71.4±12.5%（n=14）。移植瘤保留了亲本肿瘤的形态学特征、组织学结构及免疫组织化学表型，并表现出向局部组织侵袭的特性。本模型中，单细胞悬液未形成肿瘤生长。连续传代移植中，移植组织在宿主体内成瘤的平均时长为32.4±3.5周，各传代间时长相近。4例移植的宫颈发育异常组织中，有3例形成了类似宫颈发育异常组织的显微囊性结构；5例移植的正常宫颈组织中，有4例也形成了显微级宫颈组织移植物。

## 研究结论
肾被膜下移植可用于构建人类宫颈癌PDX模型，其植入率良好，且能够模拟宫颈癌的体内生物学特性。本研究首次证实，宫颈发育异常组织与正常宫颈组织可在PDX模型中形成显微级组织移植物。