Dataset Information

Trimming the Vascular Tree in Tumors: Metabolic and Immune Adaptations.

ABSTRACT: Angiogenesis, the formation of new blood vessels, has become a well-established hallmark of cancer. Its functional importance for the manifestation and progression of tumors has been further validated by the beneficial therapeutic effects of angiogenesis inhibitors, most notably ones targeting the vascular endothelial growth factor (VEGF) signaling pathways. However, with the transient and short-lived nature of the patient response, it has become evident that tumors have the ability to adapt to the pressures of vascular growth restriction. Several escape mechanisms have been described that adapt tumors to therapy-induced low-oxygen tension by either reinstating tumor growth by vascular rebound or by altering tumor behavior without the necessity to reinitiate revascularization. We review here two bypass mechanisms that either instigate angiogenic and immune-suppressive polarization of intratumoral innate immune cells to facilitate VEGF-independent angiogenesis or enable metabolic adaptation and reprogramming of endothelial cells and tumor cells to adapt to low-oxygen tension.

SUBMITTER: Allen E

PROVIDER: S-EPMC8335596 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Trimming the Vascular Tree in Tumors: Metabolic and Immune Adaptations.

Allen Elizabeth E Missiaen Rindert R Bergers Gabriele G

Cold Spring Harbor symposia on quantitative biology 20160101

Angiogenesis, the formation of new blood vessels, has become a well-established hallmark of cancer. Its functional importance for the manifestation and progression of tumors has been further validated by the beneficial therapeutic effects of angiogenesis inhibitors, most notably ones targeting the vascular endothelial growth factor (VEGF) signaling pathways. However, with the transient and short-lived nature of the patient response, it has become evident that tumors have the ability to adapt to ...[more]

PMID: 28396525

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Project description:Multiple Myeloma (MM) is an incurable plasma cell malignancy primarily localized within the bone marrow (BM). It develops from a premalignant stage, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage, smoldering MM (SMM). The mechanisms of MM progression have not yet been fully understood, all the more because patients with MGUS and SMM already carry similar initial mutations as found in MM cells. Over the last years, increased importance has been attributed to the tumor microenvironment and its role in the pathophysiology of the disease. Adaptations of MM cells to hypoxic conditions in the BM have been shown to contribute significantly to MM progression, independently from the genetic predispositions of the tumor cells. Searching for consequences of hypoxia-induced adaptations in primary human MM cells, CD138-positive plasma cells freshly isolated from BM of patients with different disease stages, comprising MGUS, SMM, and MM, were analyzed by proteome profiling, which resulted in the identification of 6218 proteins. Results have been made fully accessible via ProteomeXchange with identifier PXD010600. Data previously obtained from normal primary B cells were included for comparative purposes. A principle component analysis revealed three clusters, differentiating B cells as well as MM cells corresponding to less and more advanced disease stages. Comparing these three clusters pointed to the alteration of pathways indicating adaptations to hypoxic stress in MM cells on disease progression. Protein regulations indicating immune evasion strategies of MM cells were determined, supported by immunohistochemical staining, as well as transcription factors involved in MM development and progression. Protein regulatory networks related to metabolic adaptations of the cells became apparent. Results were strengthened by targeted analyses of a selected panel of metabolites in MM cells and MM-associated fibroblasts. Based on our data, new opportunities may arise for developing therapeutic strategies targeting myeloma disease progression.

Dataset Information

Trimming the Vascular Tree in Tumors: Metabolic and Immune Adaptations.

Publications

Trimming the Vascular Tree in Tumors: Metabolic and Immune Adaptations.

Similar Datasets

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