How tumors affect hemodynamics: a diffusion study on the zebrafish transplantable model of medullary thyroid carcinoma by Selective Plane Illumination Microscopy

Corresponding author Silvia Carra

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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 the dextran injection into the blood flow of zebrafish embryos, we found that the diffusion coefficient in embryos grafted with MTC cells was about tenfold lower compared to the same parameter in controls. Results demonstrate the potential of our approach to estimate diffusion parameters, providing valuable insights into vascular permeability changes in MTC implanted zebrafish embryos compared to 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.