The new model aims to promote a better adapted bladder cancer treatment in the future

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Microscopic image of human tumor tissue (magenta) and various immune cells: T cells (green and red), B cells (yellow) and NK cells (natural killer) (white). Activated T and B cells are represented in blue-blue, while the nuclei of all cells are shown in the darkest blue hue. Credit: Iliana Kyriaki Kerzeli

Scientists at Uppsala University have designed a new mouse model that facilitates the study of factors that contribute to the progression of human bladder cancer and the activation of the immune system as the tumor grows. Using this model, they have been able to study how proteins change before, during and after a tumor develops in the bladder wall. The study has already been published in the scientific journal PLOS ONE.

“The file was designed both to contain specific oncogenes, as they are called – mutations that can drive tumor growth – and to show a high incidence of harmful mutations, which we often see in people who receive . These harmful mutations arise due to smoking, for example, which is the main risk factor for the bladder. To the west. In this way, our model mimics how this form of cancer develops in humans, ”explains Sara Mangsbo, principal investigator and full professor in the Department of Pharmaceutical Biosciences at Uppsala University.

The main challenges of creating the first, they had to produce an organism with an immune system that functions like the human, and second, make the tumor grow in the right place and for the same reasons as in us. Previous studies and models have often used female mice as mouse models for bladder cancer, which does not fully reflect what the disease is like in humans, where cancer is three times more common in men than in women. However, women tend to have more aggressive cancer at the time of diagnosis. In the new model, both sexes have been investigated and therefore the data can be used to study how tumors develop in women and men respectively and how they both respond to various treatments.

Scientists have used the model to delve into the blood and urine of the proteomic profile (substances secreted from the tumor / immune cell area) when tumors emerge, grow, and spread. Research included examining more than 90 proteins to find out how these change in the course of tumor development and after the disease has infiltrated the muscle layer), called invasive bladder cancer.

How the gene expression of the tumor was changed from being limited to a single site until it had infiltrated the tumor was studied using “monocellular sequencing”. Thus, the researchers were able to get an idea of ​​which cells appeared and which disappeared, how the cancer cells and the surrounding tissue interacted, and what types of immune cells were being activated.

Scientists observed a different gender difference in both the type of cancer that developed in the early stages of the disease, but also that the sexes responded differently to immunotherapy, a form of treatment that activates the immune system to fight tumors.

“In the next phase of the project, the model can give us a better understanding of the types of immune cells that infiltrate tumors. And we hope that in the future it will help improve our knowledge on how to design treatment strategies specifically. adapted for men and women.For this to become a reality, studies must also be related to analysis of clinical material from biobanks, “says Mangsbo.

The work of developing the tumor model and studying it at the level of pathology, proteomics and simple is a collaboration of the Sara Mangsbo Laboratory of the Department of Pharmaceutical Biosciences; Anca Dragomir, Sven Nelander and Milena Doroszko in Immunology, Genetics and Pathology; and at the head, Ulrika Segersten and Per-Uno Malmström in Surgical Sciences.


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More information:
Iliana K. Kerzeli et al. (2021), single-cell RNAseq and longitudinal proteomic analysis of a new model of semi-spontaneous urothelial cancer reveals tumor cell heterogeneity and pretumoral urinary protein alterations, PLOS ONE. journals.plos.org/plosone/arti … journal.pone.0253178

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Uppsala University


Citation: The new model aims to promote a better adapted bladder cancer treatment in the future (2021, July 7) recovered on July 7, 2021 at https://medicalxpress.com/news/2021-07-aims -better-adapted-bladder-cancer- treatment.html

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