Assessing tumor growth and distribution in a model of prostate cancer metastasis using bioluminescence imaging
Assessing tumor growth and distribution in a model of prostate cancer metastasis using bioluminescence imaging
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DOI：
10.1007/s10585-006-9011-4
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发表时间：
2005-12-01
影响因子：
4
通讯作者：
Henry, Michael D.
中科院分区：
文献类型：
--
作者：
Drake, Justin M.;Gabriel, Curtis L.;Henry, Michael D.
生物发光成像（BLI）极大地促进了癌症动物模型的发展，可以灵敏地检测活体小鼠中表达荧光素酶的癌细胞。之前描述此类模型的努力只涉及少量动物，限制了对其性能特征的理解。我们采用 BLI 对 SCID 小鼠 (n = 85) 进行心内注射后，对前列腺癌细胞系 22Rv1 的生长和分布进行连续成像。这种方法模拟了癌细胞的血行传播，并允许研究不同器官部位的转移定植过程，尽管将癌细胞准确注射到左心室仍然具有挑战性。因此，为了预测注射成功，我们在心内注射后立即测量了胸部生物发光信号与全身生物发光信号的比率（T/WB 比率）。 T/WB比值小于0.50预测肿瘤在胸腔外的发展，而T/WB大于0.50则预测肿瘤完全在胸腔内发展，表明注射失败。使用 BLI 对渐进性肿瘤生长进行量化。肿瘤定植于多个器官部位，包括骨、肝脏和肾上腺，类似于前列腺癌患者尸检研究中的转移范围。骨中生长的肿瘤表现出混合的溶骨性和成骨性特征，引发刺状骨膜反应。凭借更准确地预测注射成功的能力，我们现在可以监测心内注射的功效，从而促进该模型的性能。
Bioluminescence imaging (BLI) has greatly facilitated the development of animal models of cancer, allowing sensitive detection of luciferase-expressing cancer cells in living mice. Previous efforts characterizing such models have involved small numbers of animals, limiting understanding of their performance features. We employed BLI to serially image the growth and distribution of a prostate cancer cell line, 22Rv1, after intracardiac injection into scid mice (n = 85). This approach models hematogenous dissemination of cancer cells and allows inquiry of the process of metastatic colonization at various organ sites, although accurately injecting cancer cells into the left ventricle remains challenging. Therefore, to predict injection success we measured the ratio of the thoracic bioluminescence signal to the whole body bioluminescence signal (T/WB ratio) immediately following intracardiac injection. A T/WB ratio less than 0.50 predicted the development of tumors outside of the thoracic cavity while a T/WB greater than 0.50 predicted the development of tumors entirely within the thoracic cavity, suggestive of a failed injection. Progressive tumor growth was quantified using BLI. Tumors colonized multiple organ sites including bone, liver, and adrenal glands resembling the spectrum of metastases in autopsy studies of patients with prostate cancer. Tumors growing in bone exhibited mixed osteolytic and osteoblastic features, eliciting a spiculated periosteal response. With the ability to more accurately predict injection success, we can now monitor efficacy of intracardiac injections facilitating the performance of this model.