H2020Индивидуална стипендия2015–2017

HGSOC · A novel approach into modeling origin and development of ovarian cancer

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-08-01 → 2017-07-31
Финансиране от ЕС: 177 599 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Стъбловите клетки в яйцеводите се анализират, за да се разбере как се развива най-смъртоносният вид рак на яйчниците. Създаването на нов модел за изследване на тези клетки помага за разработването на по-добри лекарства и методи за ранна диагностика.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

A novel approach into modeling origin and development of ovarian cancer

High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian tumors, and is the 5th leading cause of cancer related deaths among women in the western world. Recent studies have pointed at the fimbriae of the fallopian tube (FT) as one of HGSOC’s main origins. The existence of FT stem cells (SCs) has been suggested, however, their isolation and characterization have been so far elusive. Given the potential of SCs to accumulate mutations, these cells may represent one of the cellular origins of HGSOC. Xenografts and cell lines are the main platforms for ovarian cancer research. These models have many limitation including low derivation success rate and pure representation of ovarian cancer heterogeneity and hallmarks. This project is aimed at identifying SCs of the FT, evaluating their tumorigenic capacity and establishing a novel in-vitro human based platform for ovarian cancer research. A successful conclusion of this research will provide scientists an innovative tool for the study of ovarian cancer and contribute to the worldwide effort being invested in developing early detection methodologies and new drugs for ovarian cancer. Conclusions- • We have established culture system that supports long term expansion of mouse oviduct organoids. These organoids are comprised of both ciliated and secretory cells and recapitulate the tissue of origin. • Troy positive cells have high organoid forming capacity. Moreover, organoid derived from single Troy positive cells can give rise to both ciliated and secretory cells supporting their stem/progenitor identity. • We have targeted tumor driver genes using CRISPR/Cas9 technology and established new model for studding tumor development. • We have established culture system that supports long term expansion of fallopian tube and ovarian cancer organoids. These organoids recapitulate their tissue of origin can be can be genetically manipulated and serve as a platform for drug sensitivity assays.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian tumors, and is the 5th leading cause of cancer related deaths among women in the western world. Recent studies have pointed at the fimbriae of the fallopian tube (FT) as one of HGSOC’s main origins. The existence of FT stem cells (SCs) has been suggested, however, their isolation and characterization have been so far elusive. Given the potential of SCs to accumulate mutations, these cells may represent one of the cellular origins of HGSOC.This project is aimed at identifying SCs of the FT, evaluating their tumorigenic capacity and establishing a novel in-vitro human model for HGSOC development. Preliminary screening experiments of well-established SC markers have identified Lgr6 and Troy expression in the mouse oviduct. These putative SC populations will be further characterized and their capacity to maintain tissue homeostasis will be analyzed by lineage tracing experiments. Next, mouse and human organoid culture systems of FT and HGSOC will be generated. Mutating normal FT organoids in specific genes, using the CRISPR/Cas9 system, will enable following putative SCs tumorigenic capacity upon their injection to mice. Furthermore, it will generate an innovative in-vitro model of ovarian cancer development. Finally, HGSOC organoids will be used to model and follow chemotherapy resistance acquisition.

Оригинален текст от CORDIS (на английски).

Участници

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW · AMSTERDAMКоординаторНидерландия