Related Experiment Video
Updated: Sep 10, 2025
08:00
Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis
Published on: May 26, 2021
12.9K
Ischemic Injury Drives Nascent Tumor Growth Via Accelerated Hematopoietic Aging
Alexandra A C Newman1, José Gabriel Barcia Durán2, Richard Von Itter2
1Cardiovascular Research Center, Department of Medicine, New York University Langone Health, New York, New York, USA; Leon H. Charney Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA. Electronic address: https://twitter.com/aacnewman13.
JACC. Cardiooncology
|August 21, 2025
Summary
Peripheral ischemia accelerates breast cancer growth by altering hematopoietic stem cells (HSPCs), promoting myeloid cell production and suppressing antitumoral immunity. These changes are long-lasting and can be transmitted, impacting cancer progression.
Area of Science:
- Cardiovascular Biology
- Cancer Biology
- Immunology
- Stem Cell Biology
Background:
- Peripheral artery disease (PAD) increases cancer risk, with aging-related changes in hematopoietic stem and progenitor cells (HSPCs) implicated in both cardiovascular disease and cancer.
- The specific role of altered hematopoiesis in cardiovascular disease-driven tumor progression remains unclear.
Purpose of the Study:
- To investigate tumor growth following peripheral ischemia and associated changes in the HSPC bone marrow compartment.
- To uncover mechanisms by which altered hematopoiesis promotes cancer development and progression.
Main Methods:
- Monitoring mammary cancer growth in mice after hind limb ischemia (HLI) or sham surgery.
- Assessing tumor immune microenvironment, circulatory immune cells, and HSPC compartment using flow cytometry.
- Performing single-cell RNA and ATAC sequencing on bone marrow progenitors to analyze transcriptomic and epigenetic changes.
- Utilizing bone marrow transplantation to examine the functional impact of ischemia-induced HSPC reprogramming on tumor progression.
Main Results:
- Peripheral ischemia increased monocyte and neutrophil production while decreasing lymphocytes, driven by a shift towards myeloid-biased HSPCs.
- Accelerated cancer growth was observed, with tumors enriched in myeloid cells and regulatory T cells.
- Transcriptional and epigenetic analyses revealed inflammatory and aging-associated signatures in monocyte/dendritic progenitors following HLI and tumor presence.
- HLI-induced tumor growth acceleration and myeloid-skewing were transmissible via bone marrow transplantation, indicating sustained reprogramming of innate immunity.
Conclusions:
- Peripheral ischemia exacerbates inflammaging in hematopoietic stem cells.
- Long-lasting alterations in antitumoral immunity contribute to accelerated breast tumor growth.
- Ischemia-induced reprogramming of hematopoiesis represents a significant mechanism promoting cancer progression.
Related Concept Videos
02:53Adaptive Mechanisms in Cancer Cells
5.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K
01:24Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
01:01Regulation of Hematopoietic Stem Cells
3.3K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.3K
02:15Replicative Cell Senescence
3.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.7K
02:07Tumor Progression
6.5K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.5K
02:17The Tumor Microenvironment
6.8K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.8K