Optical in vivo imaging detection of preclinical models of gut tumors through the expression of integrin αVβ3.

Giulia Marelli,Roberta Avigni,Marco Erreni,Alberto Mantovani,Paola Allavena,Andrea Doni,Cecilia Garlanda

doi:10.18632/oncotarget.25826

Abstract

Optical imaging and Fluorescent Molecular Tomography (FMT) are becoming increasingly important for the study of different preclinical models of cancer, providing a non-invasive method for the evaluation of tumor progression in a relatively simple and fast way. Intestinal tumors, in particular colorectal cancer (CRC), represent a major cause of cancer-related death in Western countries: despite the presence of a number of preclinical models of intestinal carcinogenesis, there is a paucity of information about the possibility to detect intestinal tumors using fluorescent probes and optical in vivo imaging. Herein, we identify the detection of integrin αvβ3 by FMT and optical imaging as an effective approach to assess the occurrence and progression of intestinal carcinogenesis in genetic and chemically-induced mouse models. For this purpose, a commercially available probe (IntegriSense), recognizing integrin αvβ3, was injected in APC+/min mice bearing small intestinal adenomas or CRC: FMT analysis allowed a specific tumor detection, further confirmed by subsequent ex vivo imaging or conventional histology. In addition, IntegriSense detection by FMT allowed the longitudinal monitoring of tumor growth. Taken together, our data indicate the possibility to use integrin αvβ3 for the visualization of intestinal tumors in preclinical models.

Highlights

Colorectal cancer (CRC) is a frequent human neoplasia and still one of the major leading causes of cancer-related death, especially in Western Countries [1]
We excised tumor lesions or corresponding healthy mucosa from Adenomatous Polyposis Coli (APC)+/min and WT mice, respectively: mRNA analysis by q-PCR indicated that the levels of both αv and β3 subunits were significantly upregulated in small intestine tumors in comparison to corresponding healthy mucosa (Figure 1B)
When the CX3CR1 status was considered, we found that APC+/min-CX3CR1-/- mice showed a slightly but significant increased accumulation of IntegriSense750 probe compared to APC+/min-CX3CR1+/- mice both in in vivo Fluorescent Molecular Tomography (FMT) and ex vivo imaging analysis (Figure 3A, 3B and Figure 3C, 3D, respectively), confirming our previous results of increased tumor occurrence in CX3CR1-deficient mice [20, 22]

Summary

INTRODUCTION

Colorectal cancer (CRC) is a frequent human neoplasia and still one of the major leading causes of cancer-related death, especially in Western Countries [1] Both transplanted orthotopic and spontaneous mouse models of colorectal cancer are available, representing a fundamental tool to understand the biological mechanisms of tumor progression and to evaluate the efficacy of potential therapeutic approaches. The characterization of processes involved in neoplastic progression and the description of tumor features are of primary importance to determine the correct cancer staging and to identify the best prognostic, predictive or therapeutic approach for oncologic patients In this scenario, the expression of integrins, has been demonstrated to influence the prognosis in various cancer types [10]. The methodology described here may represent an evaluable tool to analyse the pathogenesis of intestinal tumors and therapeutic drug development

RESULTS

DISCUSSION

MATERIALS AND METHODS