KFU. Card publication. Development of a novel prostate Cancer-Stroma Sphere (CSS) model for In Vitro tumor microenvironment studies

KAZAN
FEDERAL UNIVERSITY

- RUS
- 中文
- ES

DEVELOPMENT OF A NOVEL PROSTATE CANCER-STROMA SPHERE (CSS) MODEL FOR IN VITRO TUMOR MICROENVIRONMENT STUDIES

Form of presentation

Articles in international journals and collections

Year of publication

2024

��

��

Authors, employees of KFU

Bulatov Emil Rafaelevich, author

Kiyamov Ayrat Gazinurovich, author

Miftakhova Regina Rifkatovna, author

Rizvanov Albert Anatolevich, author

Filina Yuliya Viktorovna, author

Bibliographic description in the original language

Rakhmatullina A.R, Zolotykh M.A, Filina Y.V, Development of a novel prostate Cancer-Stroma Sphere (CSS) model for In Vitro tumor microenvironment studies//Translational Oncology. - 2024. - Vol.44, Is.. - Art. �101930.

Annotation

Tumor employs non-cancerous cells to gain beneficial features that promote growth and survival of cancer cells. Despite intensive research in the area of tumor microenvironment, there is still a lack of reliable and reproducible in vitro model for tumor and tumor-microenvironment cell interaction studies. Herein we report the successful development of a heterogeneous cancer-stroma sphere (CSS) model composed of prostate adenocarcinoma PC3 cells and immortalized mesenchymal stem cells (MSC). The CSS model demonstrated a structured spatial layout of the cells, with stromal cells concentrated at the center of the spheres and tumor cells located on the periphery. Significant increase in the levels of VEGFA, IL-10, and IL1a has been detected in the conditioned media of CSS as compared to PC3 spheres. Single cell RNA sequencing data revealed that VEGFA was secreted by MSC cells within heterogeneous spheroids. Enhanced expression of extracellular membrane (ECM) proteins was also shown for CSS-derived MSCs. Furthermore, we demonstrated that the multicellular architecture altered cancer cell response to chemotherapeutic agents: the inhibition of sphere formation by topotecan was 74.92 ? 4.56 % for PC3 spheres and 45.95 ? 7.84 % for CSS spheres (p < 0.01), docetaxel showed 37,51? 20,88 % and 15,67? 14,08 % inhibition, respectively (p < 0.05). Thus, CSS present an effective in vitro model for examining the extracellular matrix composition and cell-to-cell interactions within the tumor, as well as for evaluating the antitumor activity of drugs.

Keywords

mesenchymal stem cells, tumor microenviroment

The name of the journal

Translational Oncology

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188605826&doi=10.1016%2fj.tranon.2024.101930&partnerID=40&md5=72e360ac3eb5e786914989676594291d

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=298201&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Bulatov Emil Rafaelevich	ru_RU
dc.contributor.author	Kiyamov Ayrat Gazinurovich	ru_RU
dc.contributor.author	Miftakhova Regina Rifkatovna	ru_RU
dc.contributor.author	Rizvanov Albert Anatolevich	ru_RU
dc.contributor.author	Filina Yuliya Viktorovna	ru_RU
dc.date.accessioned	2024-01-01T00:00:00Z	ru_RU
dc.date.available	2024-01-01T00:00:00Z	ru_RU
dc.date.issued	2024	ru_RU
dc.identifier.citation	Rakhmatullina A.R, Zolotykh M.A, Filina Y.V, Development of a novel prostate Cancer-Stroma Sphere (CSS) model for In Vitro tumor microenvironment studies//Translational Oncology. - 2024. - Vol.44, Is.. - Art. �101930.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=298201&p_lang=2	ru_RU
dc.description.abstract	Translational Oncology	ru_RU
dc.description.abstract	Tumor employs non-cancerous cells to gain beneficial features that promote growth and survival of cancer cells. Despite intensive research in the area of tumor microenvironment, there is still a lack of reliable and reproducible in vitro model for tumor and tumor-microenvironment cell interaction studies. Herein we report the successful development of a heterogeneous cancer-stroma sphere (CSS) model composed of prostate adenocarcinoma PC3 cells and immortalized mesenchymal stem cells (MSC). The CSS model demonstrated a structured spatial layout of the cells, with stromal cells concentrated at the center of the spheres and tumor cells located on the periphery. Significant increase in the levels of VEGFA, IL-10, and IL1a has been detected in the conditioned media of CSS as compared to PC3 spheres. Single cell RNA sequencing data revealed that VEGFA was secreted by MSC cells within heterogeneous spheroids. Enhanced expression of extracellular membrane (ECM) proteins was also shown for CSS-derived MSCs. Furthermore, we demonstrated that the multicellular architecture altered cancer cell response to chemotherapeutic agents: the inhibition of sphere formation by topotecan was 74.92 ? 4.56 % for PC3 spheres and 45.95 ? 7.84 % for CSS spheres (p < 0.01), docetaxel showed 37,51? 20,88 % and 15,67? 14,08 % inhibition, respectively (p < 0.05). Thus, CSS present an effective in vitro model for examining the extracellular matrix composition and cell-to-cell interactions within the tumor, as well as for evaluating the antitumor activity of drugs.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	mesenchymal stem cells	ru_RU
dc.subject	tumor microenviroment	ru_RU
dc.title	Development of a novel prostate Cancer-Stroma Sphere (CSS) model for In Vitro tumor microenvironment studies	ru_RU
dc.type	Articles in international journals and collections	ru_RU