Three-dimensional preclinical models for the study of bladder cancer
Bladder cancer is the most common tumour of the urinary apparatus and ranks 11th in incidence among all cancer in both sexes. Bladder cancer can be classified in different stage depending on its invasiveness, as it can grow deep into the bladder wall and invade the muscle layer below, or be limited to the bladder surface, and affect only epithelia; this classification is defined as staging and divide bladder cancer in two main group: Non-Muscle Invasive Bladder Cancer (NIMIBC) and Muscle Invasive Bladder Cancer (MIBC). ​Bladder tumours can be also described as high-grade (HG) or low-grade (LG), depending on their degree of abnormalities present in the structure of the tissue and of the cell itself; tumour grade indicates how quickly it is likely to grow and spread.
Figure 1: Grades and stages of bladder cancer
​​The experimental examination of bladder cancer cells could help assessing molecular profiles and metabolic features responsible for tumour invasiveness (stage) and aggressiveness (grade) to be evaluated with imaging technique. In particular, three-dimensional cellular pre-clinical models of tumours, laboratory reproductions of small avascular tumor, can provide new insights on cell modification and tissue organization, which are not possible in conventional laboratory two-dimensional models.
Figure 2: Comparison of 2 and 3 dimensional cell model
The adoption of 3D preclinical models – hereinafter referred to as “spheroids” – is a viable way to investigate biologically relevant characteristics of the disease state of tissues, while also overcoming the problem of extensive use of ex vivo tissue samples, such as biopsies from patients (which can be challenging to obtain and preserve in appropriate conditions for a meaningful study). Indeed, they recapitulate the different distribution of nutrients, wastes, the structural organization and cell-cell interaction, as well as the heterogeneous distribution of proliferating cells. When combined with biological information retrieved from deep molecular analyses, such as metabolic and genetic analysis, the analysis of spheroids by imaging techniques can enable direct correlation to diagnosis, staging and grading of major cancer diseases such as bladder cancer.
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A panel of 6 established bladder cancer cell lines was used to generate the spheroids, here represented according to grade and stage of tissue of origin, from A less aggressive, early stage, to F, more aggressive, late stage of disease, with cell line C as a bridge between the two group (low grade, late stage).