H2020Индивидуална стипендия2016–2019

PERICYTEStroma · Pericyte-derived tumor stroma – a target for cancer therapy

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

Период: 2016-10-01 → 2019-06-30
Финансиране от ЕС: 185 857 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Перицитните клетки в околността на глиобластома (агресивен мозъчен тумор) се анализират, за да се разбере как влияят на развитието му. Това е важно, защото идентифицирането на нови клетъчни мишени може да помогне за подобряване на терапията при пациентите.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Pericyte-derived tumor stroma – a target for cancer therapy

Solid tumors develop in tissue microenvironments, which contribute most of the stroma (non-malignant cells) to the tumor. The tumor stroma includes various types of cells such as vascular cells, perivascular cells, and immune cells. During recent years it has become clear that the tumor stroma is important for tumor growth, invasion, and metastasis and hence could be an attractive target for cancer therapy. Glioblastoma multiforme is the most common and highly aggressive primary brain tumor with an extremely poor prognosis. Patients have an average survival rate of 9-18 months upon diagnosis and with the available treatment options. The conventional therapies for glioblastoma are surgical removal of the tumor mass followed by radiotherapy and chemotherapy. A combination of chemo-radiotherapy with other modalities such as targeting tumor blood vessels (Bevacizumab antibody) provides only modest improvement in patient survival rates. Thus, these improved vascular-targeted therapies suggest that targeting perivascular compartments of the tumor has direct translational implications. The overall objective of this project was to study perivascular cell-derived stroma contribution to tumor with the aim to identify novel cellular targets for improving glioblastoma therapy.

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

Цел на проекта

Cancer is a devastating diagnosis since treatments to prevent a lethal outcome are limited. Tumor constitutes a complex tissue consisting of malignant cells and stromal cells. Emerging studies have shown the importance of stroma in tumor growth, invasion, and metastasis highlighting its potential as an attractive target for cancer therapy. However, the source of tumor stroma generating cells remains elusive. Generation of connective tissue is a general feature of scarring and fibrosis. While scarring is part of the wound healing response, fibrosis represents a failure to terminate tissue repair. In this context, tumors can be considered as “wounds that do not heal”. While studying spinal cord injury-induced scarring, a subpopulation of perivascular cells, type A pericytes, has been shown to be a major source of the stromal scar. Type A pericytes are embedded in the vascular wall but proliferate and leave blood vessels upon injury, differentiating into fibroblast-like cells that deposit extracellular matrix and form the stromal scar. Here, I propose to determine whether type A pericytes are a source of tumor stroma and whether blocking type A pericyte-derived stroma formation can impede cancer progression. Single cell studies to determine pericyte heterogeneity within malignant and non-malignant tissue will be performed. This characterization of heterogeneity is important to distinguish stroma-forming pericytes from the non-forming ones and from tumor cell-derived pericytes as described in Glioblastoma multiforme (GBM). Furthermore, by using combinations of pericyte reporter mice with genetic tools to manipulate pathways regulating cell proliferation and recruitment within specific pericyte subpopulations, I aim to investigate underlying mechanisms mediating pericyte-derived stroma generation. Studying stroma formation using the GBM mouse model, the proposed research intends to uncover common mechanisms of tumor stroma formation and identify new targets for therapy.

Оригинален текст от CORDIS (на английски).

Участници

KAROLINSKA INSTITUTET · STOCKHOLMКоординаторШвеция