Perspectives on the mesenchymal origin of metastatic cancer

Emerging evidence suggests that many metastatic cancers arise from cells of the myeloid/macrophage lineage regardless of the primary tissue of origin. A myeloid origin of metastatic cancer stands apart from origins involving clonal evolution or epithelial–mesenchymal transitions. Evidence is reviewed demonstrating that numerous human cancers express multiple properties of macrophages including phagocytosis, fusogenicity, and gene/protein expression. It is unlikely that the macrophage properties expressed in metastatic cancers arise from sporadic random mutations in epithelial cells, but rather from damage to an already existing mesenchymal cell, e.g., a myeloid/macrophage-type cell. Such cells would naturally embody the capacity to express the multiple behaviors of metastatic cells. The view of metastasis as a myeloid/macrophage disease will impact future cancer research and anti-metastatic therapies.

• Publication year

  2010

• Venue

  Cancer Metastasis Review

• Publication date

  2010-09-14

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1007/s10555-010-9254-zPMID 20839033PMCID 2962789
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The hallmarks of cancer

  2012cited by this paper
• Regulation of immune cell function and differentiation by the NKG2D receptor

  2011cited by this paper
• Pleural metastatic disease from glioblastoma multiforme.

  2011cited by this paper
• Macrophage diversity enhances tumor progression and metastasis.

  2010cited by this paper
• A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion

  2010cited by this paper
• The transcriptional network for mesenchymal transformation of brain tumours

  2010cited by this paper
• Influence of methotrexate and cisplatin on tumor progression and survival in the VM mouse model of systemic metastatic cancer

  2010influential reference
• Mitochondrial gateways to cancer.

  2010cited by this paper
• Macrophages, innate immunity and cancer: balance, tolerance, and diversity.

  2010cited by this paper
• Cancer as a metabolic disease

  2010influential reference
• Myeloma cell‐induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast‐myeloma hybrid cells

  2010cited by this paper
• Does the existing standard of care increase glioblastoma energy metabolism?

  2010influential reference
• Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants

  2009cited by this paper
• The transcriptional network for mesenchymal transformation of brain tumors

  2009cited by this paper
• Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the Warburg Effect

  2009cited by this paper
• Microenvironmental regulation of metastasis

  2009cited by this paper
• Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time

  2009cited by this paper
• Carcinoma of unknown primary (CUP).

  2009cited by this paper
• Carcinoma of unknown primary: Searching for the origin of metastases

  2009influential reference
• Hepatitis B virus X gene is implicated in liver carcinogenesis.

  2009cited by this paper
• The basics of epithelial-mesenchymal transition.

  2009cited by this paper
• Genetic alterations and signaling pathways in the evolution of gliomas

  2009cited by this paper
• New evidence for tumour embolism as a mode of metastasis

  2009cited by this paper
• Cell fusion as a hidden force in tumor progression.

  2009cited by this paper
• Phagocytic tumour cells.

  2009cited by this paper
• Macrophages define the invasive microenvironment in breast cancer

  2008cited by this paper
• Metastatic adenocarcinoma of unknown primary site

  2008cited by this paper
• Hepatitis B Virus HBx Protein Localizes to Mitochondria in Primary Rat Hepatocytes and Modulates Mitochondrial Membrane Potential

  2008cited by this paper
• Cancer invasion and metastasis: changing views

  2008cited by this paper
• Autophagy fights disease through cellular self-digestion

  2008cited by this paper
• Cancer-cell fusion with migratory bone-marrow-derived cells as an explanation for metastasis: new therapeutic paradigms.

  2008cited by this paper
• Metastatic cancer cell.

  2008cited by this paper
• Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis

  2008cited by this paper
• Heterogeneity of Breast Cancer Metastases: Comparison of Therapeutic Target Expression and Promoter Methylation Between Primary Tumors and Their Multifocal Metastases

  2008cited by this paper
• Xeno-cannibalism as an exacerbation of self-cannibalism: a possible fruitful survival strategy for cancer cells.

  2008cited by this paper
• S. cerevisiae induces apoptosis in human metastatic breast cancer cells by altering intracellular Ca2+ and the ratio of Bax and Bcl-2.

  2008cited by this paper
• Epithelial-to-mesenchymal transition is important to metastasis, but questions remain.

  2008cited by this paper
• The cell biology of cell-in-cell structures

  2008cited by this paper
• Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion

  2008cited by this paper
• Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation

  2008cited by this paper
• Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung

  2008cited by this paper
• Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival

  2008influential reference
• Akt-Dependent Proapoptotic Effects of Dietary Restriction on Late-Stage Management of a Phosphatase and Tensin Homologue/Tuberous Sclerosis Complex 2–Deficient Mouse Astrocytoma

  2008cited by this paper
• Heterogeneity of Drug Target Expression Among Metastatic Lesions: Lessons from a Breast Cancer Autopsy Program

  2008cited by this paper
• Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

  2008influential reference
• Plasticity of Macrophage Function during Tumor Progression: Regulation by Distinct Molecular Mechanisms1

  2008cited by this paper
• The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

  2007cited by this paper
• Inflammatory cell infiltration of tumors: Jekyll or Hyde

  2007cited by this paper
• Cannibalism: a way to feed on metastatic tumors.

  2007cited by this paper
• Yeast therapy for the treatment of breast cancer: a nude mice model study.

  2007cited by this paper
• Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis

  2007cited by this paper
• Functions and dysfunctions of mitochondrial dynamics

  2007cited by this paper
• Phagocytosis of collagen by fibroblasts and invasive cancer cells is mediated by MT1-MMP.

  2007cited by this paper
• Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma.

  2007cited by this paper
• Cell-to-cell fusion as a link between viruses and cancer

  2007cited by this paper
• The role of the organ microenvironment in the biology and therapy of cancer metastasis

  2007cited by this paper
• Cancer Statistics, 2007

  2007cited by this paper
• Cell–cell fusion

  2007cited by this paper
• A transient microenvironment loaded mainly with macrophages in the early developing human pancreas.

  2006cited by this paper
• Syncytin is involved in breast cancer-endothelial cell fusions

  2006cited by this paper
• Cell cannibalism in ductal carcinoma of breast

  2006cited by this paper
• Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy.

  2006cited by this paper
• Distinct role of macrophages in different tumor microenvironments.

  2006cited by this paper
• Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells.

  2006cited by this paper
• Tumor metastasis: mechanistic insights and clinical challenges

  2006cited by this paper
• Resolution of inflammation: the beginning programs the end

  2005cited by this paper
• Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer.

  2005cited by this paper
• Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis.

  2005cited by this paper
• Targeting energy metabolism in brain cancer: review and hypothesis

  2005cited by this paper
• Phagocytosis in the developing CNS: more than clearing the corpses.

  2005cited by this paper
• Mitochondria as functional targets of proteins coded by human tumor viruses.

  2005cited by this paper
• β1,6-Branched Oligosaccharides Are Increased in Lymph Node Metastases and Predict Poor Outcome in Breast Carcinoma

  2005cited by this paper
• Human squamous cell carcinoma of the tongue and colon undergoes apoptosis upon phagocytosis of Saccharomyces cerevisiae, the baker's yeast, in vitro.

  2005cited by this paper
• Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils

  2005cited by this paper
• Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements

  2005cited by this paper
• Tumour-cell fusion as a source of myeloid traits in cancer.

  2005cited by this paper
• Donor Y chromosome in renal carcinoma cells of a female BMT recipient: visualization of putative BMT–tumor hybrids by FISH

  2005cited by this paper
• Cancer Invasion and Metastasis

  2005cited by this paper
• Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies.

  2005cited by this paper
• The role of viruses in cell fusion and its importance to evolution, invasion and metastasis of cancer clones.

  2005cited by this paper
• Macrophage fusion: are somatic and cancer cells possible partners?

  2005influential reference
• Extra-cranial metastasis of glioblastoma multiforme presenting as acute parotitis

  2005cited by this paper
• Inflammatory cells during wound repair: the good, the bad and the ugly.

  2005cited by this paper
• Spinal and extracranial metastatic dissemination of malignant glioma.

  2005cited by this paper
• Anti-Angiogenic and Pro-Apoptotic Effects of Dietary Restriction in Experimental Brain Cancer: Role of Glucose and Ketone Bodies

  2005cited by this paper
• Integration/Interaction of Oncologic Growth

  2005cited by this paper
• Mitochondrial signaling: the retrograde response.

  2004cited by this paper
• Phagocytosis of Candida albicans by metastatic and non metastatic human breast cancer cell lines in vitro.

  2004cited by this paper
• Stem cell plasticity: from transdifferentiation to macrophage fusion

  2004cited by this paper
• Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification

  2004cited by this paper
• Invasiveness of primary brain tumors

  2004cited by this paper
• Myelomonocytic cells are sufficient for therapeutic cell fusion in liver

  2004cited by this paper
• Spontaneous fusion between cancer cells and endothelial cells

  2004cited by this paper
• Hemophagocytic, Non-Secretory Multiple Myeloma

  2004cited by this paper
• A role for ezrin in a neglected metastatic tumor function.

  2004cited by this paper
• Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners.

  2004cited by this paper
• Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors

  2004cited by this paper
• Nonmetastatic tumor cells acquire metastatic properties following somatic hybridization with normal cells

  2004cited by this paper
• Donor DNA in a renal cell carcinoma metastasis from a bone marrow transplant recipient

  2004cited by this paper
• The somatic mutation theory of cancer: growing problems with the paradigm?

  2004cited by this paper

• The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer

  2025cites this paper
• Are Mitochondria the True Origin of Cancer? A Hypothesis-Driven Perspective

  2025cites this paper
• Histopathological Features and Diagnosis of Breast Cancer

  2024cites this paper
• Metabolic factors associated with the prognosis of oligometastatic patients treated with stereotactic body radiotherapy

  2023cites this paper
• Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background

  2022cites this paper
• Cancer as a form of life: Musings of the cancer and evolution symposium.

  2021cites this paper
• Cancer and stem cells

  2021cites this paper
• Formation of Large Intracellular Actin Networks Following Plasmonic Cell Fusion

  2021cites this paper
• Can the Mitochondrial Metabolic Theory Explain Better the Origin and Management of Cancer than Can the Somatic Mutation Theory?

  2021cites this paper
• Possible Nutrition-Related Mechanisms of Metabolic Management in Cancer Treatment

  2021cites this paper
• The stressful tumour environment drives plasticity of cell migration programmes, contributing to metastasis

  2020cites this paper
• Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

  2020cites this paper
• Significant Neutrophilic Emperipolesis in Squamous Cell Carcinoma

  2018cites this paper
• Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

  2018cites this paper
• Press-pulse: a novel therapeutic strategy for the metabolic management of cancer

  2017cites this paper
• Are Macrophages Responsible for Cancer Metastasis

  2016cites this paper
• 4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.

  2016cites this paper
• Bis(monoacylglycero)phosphate as a Macrophage Enriched Phospholipid

  2015cites this paper
• Bis(monoacylglycero)phosphate (BMP), a novel macrophage associated phospholipid: Implications in gangliosidoses and cancer

  2015cites this paper
• Cancer as a mitochondrial metabolic disease

  2015cites this paper
• Hafnium oxide nanoparticles: toward an in vitro predictive biological effect?

  2014cites this paper
• Should EMT of Cancer Cells Be Understood as Epithelial-Myeloid Transition?

  2014cites this paper
• Targeting Cancer Metabolism with Ketosis and Hyperbaric Oxygen

  2014cites this paper
• Cancer as a metabolic disease: implications for novel therapeutics

  2013cites this paper
• Gene expression profiles in canine mammary carcinomas of various grades of malignancy

  2013cites this paper
• On the origin of cancer metastasis.

  2013cites this paper
• Nothing in Cancer Biology Makes Sense Except in the Light of Evolution

  2012cites this paper
• Genes, Respiration, Viruses, and Cancer

  2012cites this paper
• The Tumor Mitochondrial Lipidome and Respiratory Bioenergetic Insufficiency

  2012cites this paper
• Respiratory Dysfunction in Cancer Cells

  2012cites this paper
• Metabolic Management of Cancer

  2012cites this paper
• Energetics of Normal Cells and Cancer Cells

  2012cites this paper
• Mechanisms of AIDS-related lymphoma pathogenesis

  2012cites this paper
• Cancer Treatment Strategies

  2012cites this paper
• Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?

  2012cites this paper
• Transformation of non-tumor host cells during tumor progression: theories and evidence

  2012cites this paper
• Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis

  2012cites this paper
• Neutrophil-tumor cell phagocytosis (cannibalism) in human tumors: an update and literature review.

  2012cites this paper
• Tumor‐promoting macrophages induce the expression of the macrophage‐specific receptor CD163 in malignant cells

  2012cites this paper
• Establishment of animal model for the analysis of cancer cell metastasis during radiotherapy

  2012cites this paper
• The VM Mouse Model of Glioblastoma Multiforme

  2012cites this paper
• Carcinoma Metastasis-An Approach to Models

  2011cites this paper
• Inception of the metastatic phenotype by macrophage-cancer cell fusion.

  2011cites this paper
• Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme?

  2011cites this paper
• The Restricted Ketogenic Diet : An Alternative Treatment Strategy for Glioblastoma Multiforme a report

  2011cites this paper
• Modeling sarcomagenesis using multipotent mesenchymal stem cells

  2011cites this paper
• Differential expression of the 18 kDa translocator protein (TSPO) by neoplastic and inflammatory cells in mouse tumors of breast cancer.

  2011cites this paper
• International Journal of Molecular Sciences the Dark Side of Cell Fusion

  year unknowncites this paper