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Establishment and Characterization of Bladder Cancer Organoids

Medle, Benjamin (2021) MOBN03 20202
Degree Projects in Molecular Biology
Popular Abstract
Miniature bladder tumors in a 3D cell culture

Bladder cancer is a common cancer type and represents a complex disease that causes high mortality if not treated properly. To find new treatments and optimize current therapies, expanding research model systems is important. The aim of this Master’s Project was to establish and optimize a newly popularized organoid method on bladder cancer cells.

Our understanding of bladder cancer has improved significantly over the past few years with new technologies and bioinformatic approaches. Bladder cancer can now be divided into subtypes with distinct properties, for example, they express variable drug targetable genes and lead to different prognoses. However, the small range of tumor research... (More)
Miniature bladder tumors in a 3D cell culture

Bladder cancer is a common cancer type and represents a complex disease that causes high mortality if not treated properly. To find new treatments and optimize current therapies, expanding research model systems is important. The aim of this Master’s Project was to establish and optimize a newly popularized organoid method on bladder cancer cells.

Our understanding of bladder cancer has improved significantly over the past few years with new technologies and bioinformatic approaches. Bladder cancer can now be divided into subtypes with distinct properties, for example, they express variable drug targetable genes and lead to different prognoses. However, the small range of tumor research models is slowing the development of new therapeutics. First, let’s see what models are currently available.

Animals, such as mice, have the most resemblance to human biology and have historically provided the basis for research of biological processes and development of drugs. But their use is restricted and ethically problematic. This is why classical cell lines are used for extensive trials instead. Unfortunately, 2D cultures do not represent the true cellular interactions in tissues. Here is where 3D models come into play! Such 3D forms, also known as organoids are a great new addition to the standard models. Organoids are multicellular structures that can achieve the complexity of organs resembling the ones in the human body. Although still in their beginnings and far behind the established standards, organoids offer a way to answer complex research questions. Organoids have a promising future in drug development as well as personalized medicine.

The first goal of the project was establishing a system to produce human bladder cancer organoids. We aimed to generate organoids representative of the original tumors from patients and to see if organoids are able to change their identity. As primary tumor tissue, we used patient-derived tumors grown in mice. The majority of the project included optimization of organoid culturing with a 55% success rate of producing organoids. We established a variety of organoids with phenotypical diversity within and among bladder cancer subtypes. Then, we molecularly characterized obtained models with widely utilized techniques to quantify gene activity and protein levels (qRT-PCR and immunohistochemistry). Finally, by exposing the organoids to distinct growth conditions, we showed that some tumors lost their capacity to differentiate. Ultimately this established method can now be used to further study bladder cancer.


Master’s Degree Project in Molecular Biology, 60 credits, 2020/21
Department of Biology, Lund University

Supervisor: Carina Bernardo
Department of Clinical Science, Division of Oncology (Less)
Please use this url to cite or link to this publication:
author
Medle, Benjamin
supervisor
organization
course
MOBN03 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9067414
date added to LUP
2021-10-28 09:39:08
date last changed
2021-10-28 09:39:08
@misc{9067414,
  author       = {{Medle, Benjamin}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Establishment and Characterization of Bladder Cancer Organoids}},
  year         = {{2021}},
}