A patient derived xenograft model of cervical cancer and cervical dysplasia
A patient derived xenograft model of cervical cancer and cervical dysplasia
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DOI：
10.1371/journal.pone.0206539
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发表时间：
2018-10-26
期刊：
影响因子：
3.7
通讯作者：
Gargett, Caroline E.
中科院分区：
文献类型：
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作者：
Larmour, Luke, I;Cousins, Fiona L.;Gargett, Caroline E.
方法将12例宫颈鳞癌、1例宫颈腺癌、1例宫颈腺鳞癌、7例宫颈异型增生活检组织和正常宫颈组织移植于免疫功能低下的NOD/SCID/γ小鼠肾包膜下。收获所得的肿瘤，并将其部分连续移植到新的受体小鼠中，进行多达三次体内传代。通过免疫组化检查亲本和异种移植肿瘤的p16（INK 41）、HPV和CD-45。单细胞悬浮液的混合小鼠和人类，或人类只有细胞群体也transplanted.ResultsThe总体植入率为原发性宫颈癌PDX模型为71.4 +/- 12.5%（n = 14）。肿瘤保持了母体肿瘤的形态学、组织结构和免疫组化特征，并表现出对局部组织的侵袭性。单细胞悬浮液在该模型中不产生肿瘤生长。移植组织在动物体内产生肿瘤的平均时间长度（32.4 +/- 3.5周）在连续移植之间相似。四个异种移植的宫颈发育不良组织中有三个产生了类似于发育不良宫颈组织的显微镜下囊性结构。正常的宫颈组织（4 5异种移植）也开发了显微镜下的宫颈组织grafts.ConclusionThe肾包膜下可用于PDX模型的人宫颈癌具有良好的植入率和能力，在体内的宫颈癌的特点模型。这是我们第一次在PDX模型中证明宫颈发育不良和正常宫颈组织产生显微组织。
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 p16(INK41), 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.