Personal ViewThe seed and soil hypothesis: vascularisation and brain metastases
Section snippets
Neoplastic angiogenesis
To produce metastases, tumour cells must complete a series of sequential and selective steps.4, 10 Failure to complete even one step eliminates the cells from the process.11 Previous studies have shown that to produce brain metastases, tumour cells must reach the vasculature of the brain, attach to the endothelial cells of the microvasculature, extravasate into the parenchyma, proliferate (in response to growth factors), and induce the formation of new blood vessels.12, 13
The growth and spread
Neovascularisation and vascular remodelling in brain metastases
Since the seminal observation of Weidner,28 many reports have suggested that the mean vessel density (MVD) within or at the periphery of spontaneous and artificially induced tumours in mice and rats, and within clinical specimens of human neoplasms, correlates with the aggressiveness of the disease. However, this generalisation does not extend to experimental brain metastases. In the tumour model we have used, tumour cells injected into the internal carotid artery of nude mice resulted in
Location of dividing tumour cells in relation to the vasculature
The diffusion coefficient of oxygen within tissues is about 150–200 μm.39, 40 Since cell viability depends on oxygen, we wished to find out whether the location of dividing or apoptotic tumour cells within brain metastases was related to distance from the nearest blood vessel. Because the growth of discrete, focal, experimentally induced brain metastases was associated with fewer but larger blood vessels per unit area, we also wanted to know whether the proximity of tumour cells to blood
Location of apoptotic tumour cells in relation to vasculature
To assess the distance of apoptotic cells from the nearest blood vessel, we sequentially labelled sections of tumour tissue for the CD31 antigen, and then used an end-labelling assay (terminal-uridine nick-end labelling, or TUNEL) to detect apoptotic cells.44 The distance of apoptotic cells from the blood vessel was assessed with the EDM.45 Apoptotic cells (TUNEL-positive) in autochthonous human lung-cancer brain metastases (Figure 3b) and KM12C brain metastases (Figure 3d) were mostly located
The blood-brain barrier in brain metastasis
The microvasculature of the brain parenchyma is lined with a continuous, non-fenestrated endothelium with tight junctions and little pinocytic vesicle activity.46, 47 This structure, designated the blood-brain barrier (BBB), limits the entrance of circulating macromolecules into the brain parenchyma. The BBB and the lack of a lymphatic system maintain the brain as an immunologically privileged site48 and protect the brain against the entry of most drugs and invasion by microorganisms.49
References (57)
The distribution of secondary growths in cancer of the breast
Lancet
(1889)- et al.
Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumour angiogenesis
Microvasc Res
(1996) Tie1 and Tie2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth
Microvasc Res
(1998)Delivery of molecular and cellular medicine to solid tumours
Adv Drug Del Rev
(2001)Management of central nervous system metastases
Semin Oncol
(1977)- et al.
Surgical treatment of metastatic brain tumours
J Neurooncol
(1996) - et al.
Metastasis results from preexisting variant cells within a malignant tumour
Science
(1977) Critical factors in the biology of human cancer metastasis: twenty-eighth GHA Clowes Memorial Award Lecture
Cancer Res
(1990)Modulation of the organ microenvironment for the treatment of cancer metastasis (editorial)
J Natl Cancer Inst
(1995)Selection of successive tumour lines for metastasis
Nature
(1973)
Evidence for the clonal origin of spontaneous metastasis
Science
Clonal origin of metastasis in B16 murine melanoma: a cytogenetic study
J Natl Cancer Inst
Molecular biology of cancer: invasion and metastasis
Different deficiencies in the prevention of tumorigenic-low-metastatic murine K-1735 melanoma cells from producing metastasis
J Natl Cancer Inst
Site-specific metastasis of mouse melanomas and a fibrosarcoma in the brain or meninges of syngeneic animals
Cancer Res
Critical factors regulating site-specific brain metastasis of murine melanomas
Int J Oncol
Clinical applications of research on angiogenesis
N Engl J Med
Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation
Cell
Angiogenesis in cancer and other diseases
Nature
Anti-angiogenesis therapy and strategies for integrating it with adjuvant therapy
Cancer Res
Mechanisms of angiogenesis
Nature
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Nature
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene
Nature
Tumour cells secrete a vascular permeability factor that promotes accumulation of ascites fluid
Science
Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells
Biochem Biophys Res Commun
Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells
J Cell Physiol
Regulation of distinct steps of angiogenesis by different angiogenic molecules
Int J Oncol
Intracerebral tumour-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189
Proc Natl Acad Sci USA
Cited by (366)
Machine-Learning-Aided Prediction of Brain Metastases Development in Non–Small-Cell Lung Cancers
2023, Clinical Lung CancerGraphdiyne oxide nanosheets exert anti-lymphoma effect by killing cancer stem cells and remodeling tumor microenvironment
2022, Nano TodayCitation Excerpt :The immunosuppressive TME is critical for maintaining the survival and growth of malignant lymphoma cells, subclonal evolution, and drug resistance [11]. Based on the "seed and soil" theory [12–15], cancer stem cells (CSC) and TME form a complex dynamic regulatory network that facilitates the co-evolution and provides necessary signals for tumor initiation, survival, proliferation, immune escape, and drug resistance. Moreover, lymphoma cells are regulated by the microenvironment and can also recruit other stromal cells and immune cells to transform the microenvironment [10].
The role of magnetic hyperthermia in heating-based oncological therapies
2021, Magnetic Materials and Technologies for Medical Applications