Bioluminescence imaging to monitor bladder cancer cell adhesion in vivo: a new approach to optimize a syngeneic, orthotopic, murine bladder cancer model

Abstract

OBJECTIVE To improve the orthotopic murine bladder cancer model by using bioluminescent (BL) MB49 tumour cells for noninvasive in vivo monitoring of tumour growth and to examine the efficacy of integrin receptor‐blocking oligopeptides on preventing tumour cell adhesion in this improved bladder cancer model. MATERIALS AND METHODS The capacity of oligopeptide combinations to interfere with tumour cell adhesion was assessed in vivo in a syngeneic, orthotopic, murine bladder cancer model. Tumour outgrowth was monitored noninvasively by bioluminescence imaging (BLI) after administration of luciferase‐expressing MB49LUC bladder cancer cells. The presence of tumour cells was verified histologically and immunohistochemically on paraffin wax‐embedded sections of excised bladders. RESULTS Anti‐adhesive oligopeptides effectively inhibited tumour outgrowth. BLI detected tumour cells at an early stage when there were no clinical signs of cancer in any of the mice. The technique has high sensitivity in detecting tumour cell implantation, but is less reliable in assessing tumour volume in advanced‐stage disease due to light attenuation in large tumours. CONCLUSIONS Peptides targeting adhesion molecules prevent attachment of bladder cancer cells to the injured bladder wall. BLI is a sensitive method for detecting luminescent bladder cancer cells in an orthotopic mouse model.

Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer

“…1B) due to presence of necrotic tumors and/or low tumor-perfusion, preventing tumor-penetration of the injected luciferin. 13 A classical schedule for intravesical treatment in this model start 1 day after tumor implantation and is given four-times once a week. 12 The first intravesical instillation results in an initially delayed tumor-growth (see tumor bioluminescence at day 8 in Fig.…”

“…Tumor growth was monitored by bioluminescence 15 min after intraperitoneal injection of D-luciferin (Promega, 150 mg/g of body weight) in the Xenogen imaging system (Xenogen/IVIS Caliper Life Science, kindly provided by cellular imaging facility, CIF/UNIL, Lausanne, Switzerland). Bioluminescence monitoring of MB49-luc tumor is very efficient for assessing tumor establishment and growth during the first 3 weeks, however, uncontrolled loss of luminescence of the growing tumors can then often appear, 13 requiring additional monitoring by palpation, hematuria and overall health status of the mice, that were euthanized in case of >15% weight-loss.…”

Fractionated intravesical radioimmunotherapy with213Bi-anti-EGFR-MAb is effective without toxic side-effects in a nude mouse model of advanced human bladder carcinoma

“…Therefore, bioluminescence imaging mainly can be used as a qualitative technique with limitations in the quantification of more advanced tumor stages. 29 In our study light emissions over ROIs were used only to analyze tumor development of one and the same animal before and after treatment (Fig. 5).…”

A Single Intravesical Instillation of VAX014 Inhibits Orthotopic Superficial Bladder Tumor Implantation to Increase Survival

“…Re-seeding may be facilitated, in part, by the interaction of tumor cell integrins with extracellular matrix (ECM) components including fibronectin, laminin, and collagen, all of which are likely to be exposed at the surgical site following resection. Previous reports have indicated that specific mammalian integrins, particularly integrin heterodimer family members alpha3beta1 (α3β1) and alpha5beta1 (α5β1), are implicated as being required for the attachment of tumor cells to the ECM and establishment of tumors in the urothelium in vivo (11)(12)(13).…”