How Tumors Affect Hemodynamics: A Diffusion Study on the Zebrafish Transplantable Model of Medullary Thyroid Carcinoma by Selective Plane Illumination Microscopy

肿瘤如何影响血液动力学:利用选择性平面照明显微镜对斑马鱼髓样甲状腺癌移植模型进行扩散研究

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Abstract

Medullary thyroid carcinoma (MTC), a rare neuroendocrine tumor comprising 3-5% of thyroid cancers, arises from calcitonin-producing parafollicular C cells. Despite aggressive behavior, surgery remains the primary curative treatment, with limited efficacy reported for radiotherapy and chemotherapy. Recent efforts have explored the pathogenetic mechanisms of MTC, identifying it as a highly vascularized neoplasm overexpressing pro-angiogenic factors. Building on the established benefits of zebrafish embryos, we previously created an in vivo MTC xenograft platform that allows real-time observation of tumor-induced angiogenesis and evaluation of the anti-angiogenic effects of tyrosine kinase inhibitors. In this study, we present a method using selective plane illumination microscopy (SPIM) to characterize vascular permeability in these xenografted embryos. Taking advantage of dextran injections into the blood flow of zebrafish embryos, we found that the diffusion coefficient in embryos grafted with MTC cells was about tenfold lower compared with the same parameter in controls. The results demonstrate the potential of our approach to estimate diffusion parameters, providing valuable insights into vascular permeability changes in MTC-implanted zebrafish embryos compared with controls. Our study sheds light on the intricate vascular biology of MTC, offering a promising tool for future investigations into tumor-induced angiogenesis and therapeutic strategies in diverse neoplasms.

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