DOI: 10.5281/zenodo.14016517
title: How tumors affect hemodynamics: a diffusion study on the zebrafish transplantable model of medullary thyroid carcinoma by Selective Plane Illumination Microscopy

description: Corresponding author Silvia Carra

Contact email s.carra@auxologico.it

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.

 
description: Following files have been uploaded:

rhodamine diffusion1.opju

This file contains examples of fluorescent dextran intensity profiles over time measured in jellified agarose solution, as well as the trend of the half value time as a function of the distance of the observation volume from the injection volume for control embryos and for three different xenotransplanted embryos. To be opened with the program OriginLab Pro.

rhodamine diffusion2.opju

This file contains fluorescent dextran intensity profiles versus time measured at increasing distances from the SIV plexus for a control zebrafish embryo. To be opened with the program OriginLab Pro.

Rhodamine diffusion3.opju

This file contains examples of fluorescent dextran intensity profiles on different xenografted zebrafish samples at different distances from the injection point. To be opened with the program OriginLab Pro.

Optical cross sections.opju

This file contains example of the profiles of the cross section of the light sheet image acquired by means of a reflecting mirror (640x512 pixels, 880µm×700µm). To be opened with the program OriginLab Pro.

Diffusion-related simulations.opju

This file contains following data:

-Simulations of the time trend of the concentration for increasing values of the distance between the injection and observation sites

-Simulation of the concentration (and fluorescence) decay as a function of time for the case in which the injection was done at t = 2000 s prior the start of the observation

-Simulation of the relationship between the two estimates of the spread of the concentration wave as a function of the diffusion coefficient

-Simulations of the half decay time as a function of the distance of observation from the injection volume