Summary
The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing ‘unspecific’ (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's ‘seed and soil’ hypothesis of metastasis.
Similar content being viewed by others
References
Paget S: The distribution of secondary growths in cancer of the breast. Lancet 1: 571–573, 1989
Hart IR: ‘Seed and soil’ revisited: mechanisms of site-specific metastasis. Cancer Metastasis Rev 1: 5–16, 1982
Kieran MW, Longenecker BM: Organ specific metastasis with specific reference to avian systems. Cancer Metastasis Rev 2: 165–182, 1983
Weiss L: Principles of Metastasis. Academic Press, New York, 1985
Schirrmacher V: Cancer metastasis: experimental approaches, theoretical concepts and impacts for treatment strategies. Adv Cancer Res 43: 1–73, 1985
Auerbach R: Patterns of tumor metastasis: organ selectivity in the spread of cancer cells. Lab Invest 58: 361–364, 1988
Nicolson GL: Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev 7: 143–188, 1988
Nicolson GL: Cancer Metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites. Biochim Biophys Acta 948: 175–224, 1988
Sher BT, Bargatze R, Holzmann B, Gallatin WM, Mathews D, Wu N, Picker L, Butcher EC, Weissman IL: Homing receptors and metastasis. Adv Cancer Res 51: 361–390, 1988
Zetter BR: The cellular basis of site-specific tumor metastasis. New Engl J Med 322: 605–612, 1990
Greene HSN, Harvey EK: The relationship between the dissemination of tumor cells and the distribution of metastases. Cancer Res 24: 799–811, 1964
Alby L, Auerbach R: Differential adhesion of tumor cells to capillary endothelial cellsin vitro. Proc Natl Acad Sci USA 81: 5739–5743, 1984
Roos E, Tulp A, Middelkoop OP, van dePavert IV: Interactions between lymphoid tumor cells and isolated liver endothelial cells. J Natl Cancer Inst 72: 1173–1180, 1984
Auerbach R, Lu WC, Pardon E, Gumkowski F, Kaminska G, Kaminska M: Specificity of adhesion between murine tumor cells and capillary endothelium: anin vitro correlate of preferential metastasisin vivo. Cancer Res 47: 1492–1496, 1987
Pauli BU, Lee CL: Organ preference of metastasis: the role of organ-specifically modulated endothelial cells. Lab Invest 58: 379–387, 1988
Rice GE, Gimbrone MAJr, Bevilacqua MP: Tumor cell-endothelial cell interactions. Increased adhesion of human melanoma cells to activated vascular endothelium. Am J Pathol 133: 204–210, 1988
Rice GE, Bevilacqua MP: An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science 246: 1303–1306, 1989
Fishman AP: Endothelium: a distributed organ of diverse capabilities. Ann NY Acad Sci 401: 1–8, 1982
Simionescu N, Simionescu M, Palade GE: Differentiated microdomains on the luminal surface of the capillary endothelium. I. Preferential distribution of anionic sites. J Cell Biol 90: 605–613, 1981
Simionescu M, Simionescu N, Palade GE: Differentiated microdomains on the luminal surface of the capillary endothelium: distribution of lectin receptors. J Cell Biol 94: 406–413, 1982
Simionescu M, Simionescu N, Palade GE: Biochemically differentiated microdomains of the cell surface of capillary endothelium. Ann NY Acad Sci 401: 9–24, 1982
Robinson AP, White TM, Mason DW: MRC OX-43: a monoclonal antibody which reacts with all vascular endothelium in the rat except that of brain capillaries. Immunology 57: 231–237, 1986
Gumkowski F, Kaminska G, Kaminska M, Norrissey LW, Auerbach R: Heterogeneity of mouse vascular endothelium:in vitro studies of lymphatic, large vessel and microvascular endothelial cells. Blood Vessels 24: 11–23, 1987
Cotran RS: New roles for the endothelium in inflammation and immunity. Am J Pathol 129: 407–413, 1987
Jutila MA, Lewinsohn DM, Lakey Bery E, Butcher EC: Homing receptors in lymphocyte, neutrophil, and monocyte interactions with endothelial cells. In: Springer TA (ed) Structure, Function, and Regulation. Springer Verlag, New York, 1988, pp 227–235
Belloni PN, Nicolson GL: Differential expression of cell surface glycoproteins on various organ-derived microvascular endothelia and endothelial cell cultures. J Cell Physiol 136: 398–410, 1988
Butcher EC: Cellular and molecular mechanisms that direct leukocyte traffic. Am J Pathol 136: 3–11, 1990
Pober JS, Bevilacqua MP, Mendrick DL, Lapierre LA, Fiers W, Gimbrone MAJr: Two distinct monokines, interleukin-1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 136: 1680–1687, 1986
Bevilacqua MP, Stengelin S, Gimbrone MAJr, Seed B: Endothelial leukocyte adhesion molecule-1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243: 1160–1165, 1989
Stoolman LM: Adhesion molecules controlling lymphocyte migration. Cell 56: 907–910, 1989
Rupnick MA, Carey A, Williams SK: Phenotypic diversity in cultured cerebral microvascular endothelial cells. In Vitro Cell Dev Biol 24: 435–444, 1988
Holthöfer H: Ulex europaeus I lectin as a marker for tumors derived from endothelial cells. J Histochem Cytochem 31: 531–537, 1983
Mills AN, Haworth SG: Changes in lectin binding patterns in the developing pulmonary vasculature of the pig lung. J Pathol 149: 191–199, 1986
Ponder BAJ, Wilkinson MM: Organ-related differences in binding of Dolichos biflorus agglutinin to vascular endothelium. Dev Biol 96: 535–541, 1983
Soda R, Ravassol M: Mapping of the bone marrow sinus endothelium with lectins and glycosylated ferritins: identification of differential microdomains and their functional significance. J Ultrastruct Res 84: 299–310, 1983
Irie S, Tavassoli M: Mapping of the rat liver endothelial membrane with lectins and glycosylated ferritins. Am J Anat 177: 403–413, 1986
Madri JA, Williams SK, Wyatt T, Mezzio C: Capillary cell culture: Phenotypic modulation by matrix components. J Cell Biol 97: 153–165, 1983
Madri JA, Pratt BM, Tucker AM: Phenotypic modulation of endothelial cells by transforming growth factor-β depends upon the composition and organization of the extra-cellular matrix. J Cell Biol 106: 1375–1384, 1988
Carley WW, Milici AJ, Madri JA: Extracellular matrix specificity for differentiation of capillary endothelial cells. Exp Cell Res 178: 426–434, 1988
Ingber DE, Folkman J: How does extracellular matrix control capillary morphogenesis. Cell 58: 803–805, 1989
Milici AJ, Furie MB, Carley WW: The formation of fenestrations and channels by capillary endotheliumin vitro. Proc Natl Acad Sci USA 82: 6181–6185, 1985
Augustin-Voss HG, Johnson RC, Pauli BU: Modulation of endothelial cell surface glycoconjugate expression by organ-derived biomatrices. FASEB J 4: A1018, 1990
Madri JA, Stenn KS: Aortic endothelial cell migration. I. Matrix requirements and composition. Am J Pathol 106: 180–186, 1982
Kramer RH, Bensch KG, Davison KG, Karasek MA: Bassl lamina formation by cultured microvascular endothelial cells. J Cell Biol 99: 692–698, 1984
Form DM, Pratt BM, Madri JA: Endothelial cell proliferation during angiogenesis.In vitro modulation by basement membrane components. Lab Invest 55: 521–530, 1986
Moscatelli D: Metabolism of receptor-bound and matrixbound basic fibroblast growth factor by bovine capillary endothelial cells. J Cell Biol 107: 753–759, 1988
Eldridge CF, Bunge MB, Bunge RP, Wood PM: Differentiation of axon-related Schwann cellsin vitro. I. Ascorbid acid regulates basal lamina assembly and myelin formation. J Cell Biol 105: 1023–1034, 1987
Eldridge CF, Bunge MB, Bunge RP: Differentiation of axon-related Schwann cellsin vitro. II. Control of myelin formation by basal lamina. J Neurochem 9: 625–638, 1989
Bissel MJ, Hall HG, Parry G: How does the extracellular matrix direct gene expression? J Theor Biol 99: 31–68, 1982
Reid L, Morrow B, Jubinsky P, Schwartz E, Gatmaitan Z: Regulation of growth and differentiation of epithelial cells by hormones, growth factors, and substrates of extracellular matrix. Ann NY Acad Sci 372: 354–370, 1981
Gatmaitan Z, Jefferson DM, Ruiz-Opaza N, Biempica L, Arias IM, Dudas G, Leinwand LA, Reid LM: Regulation of growth and differentiation of a rat hepatoma cell line by the synergistic interaction of hormones and collagenous substrate. J Cell Biol 97: 1179–1190, 1983
Wicha MS, Lowrie G, Kohn E, Bagavandoss P, Mahn T: Extracellular matrix promotes mammary epithelial growth and differentiationin vitro. Proc Natl Acad Sci USA 79: 3213–3217, 1982
Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I: A heparin-binding angiogenic protein-basic fibroblast growth factor—is stored within basement membrane. Am J Pathol 130: 393–400, 1988
Cerra RF, Nathanson DN: Organ-specific chemotactic factors present in lung extracellular matrix. J Surg Res 46: 422–426, 1989
Fajarda LF: The complexity of endothelial cells. Am J Clin Pathol 92: 241–250, 1989
Jaffe EA: Cell biology of endothelial cells. Human Pathol 18: 234–239, 1987
Turner RR, Beckstead JH, Wanke RA, Wood GS: Endothelial cell phenotypic diversity. Am J Clin Pathol 87: 569–575, 1987
Tohgo A, Tanaka NG, Ogawa H: Platelet-aggregating activities of metastasizing tumor cells IV. Effects of cell surface modification on thrombin generation, platelet aggregation and subsequent lung colonization. Invasion Metastasis 6: 58–68, 1986
Nicolson GL: Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem 30: 214–220, 1982
Pauli BU, Johnson RC, El-Sabban ME: Organotypic endothelial cell surface molecules mediate organ preference of metastasis. In: Simionescu N, Simionescu M (eds) Endothelial Cell Dysfunction. Plenum Press, New York, 1990, (in press)
Nicolson GL, Belloni PN, Tressler DJ, Dulski K, Inoue T, Cavanough PG: Adhesive, invasive, and growth properties of selected metastatic variants of a murine large cell lymphoma. Invasion Metastasis 9: 102–116, 1989
Folkman J, Haudenschild CC, Zetter BR: Long-term culture of capillary endothelial cells. Proc Natl Acad Sci USA 76: 5217–5221, 1979
Bowman PD, Betz AL, Ar D, Wolinsky JS, Penney JB, Shivers RR, Goldstein GW: Primary culture of capillary endothelium from rat brain. In Vitro 17: 353–362, 1981
Carson MP, Haudenschild CC: Microvascular endothelium and pericytes: High yield, low passage cultures. In Vitro Cell Dev Biol 22: 344–354, 1986
Orr FW, Adamson IY, Young L: Pulmonary inflammation generates chemotactic activity for tumor cells and promotes lung metastasis. Am Rev Respir Dis 131: 607–611, 1985
Van denBrenk HAS, Stone M, Kelley H, et al.: Promotion of growth of tumor cells in acutely inflamed tissues. Br J Cancer 30: 246–260, 1984
Weiss L, Orr FW, Honn KV: Interactions between cancer cells and the microvasculature: a rate-regulator of metastasis. Clin Exp Metastasis 7: 127–167, 1989
Lafrenie RM, Podor TJ, Buchanan MR, Orr FW: Interleukin-1α induced vitronectin receptor expression and tumor endothelial cell adhesion. FASEB J 4: A1134, 1990
Stamper HBJr, Woodruff JJ: Lymphocyte homing into lymph nodes:in vitro demonstration of the selective affinity of recirculating lymphocytes to high endothelial venules. J Exp Med 144: 828–833, 1976.
Butcher EC, Scollay RG, Weissman IL: Lymphocyte adherence to high endothelial venules: characteristics of a modifiedin vitro assay and examination of the binding of syngeneic and allogeneic lymphocyte populations. J Immunol 123: 1996–2003, 1979
Bargatze RF, Wu NW, Weissman IL, Butcher EC: High endothelial venule binding as a predictor of the dissemination of passaged murine lymphomas. J Exp Med 166: 1125–1131, 1987
Streeter PR, Rouse BTN, Butcher EC: Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J Cell Biol 107: 1853–1862, 1988
Streeter PR, Berg EL, Rouse BN, Bargatze RF, Butcher EC: A tissue-specific endothelial cell molecule involved in lymphocyte homing. Nature 331: 41–46, 1988
Berg EL, Goldstein LA, Jutila MA, Nakache M, Picker IJ, Streeter PR, Wu NW, Zhou D, Butcher EC: Homing receptors and vascular addressins: Cell adhesion molecules that direct lymphocyte traffic. Immunol Rev 108: 5–18, 1989
Gallatin WM, Weissman IL, Butcher EC: A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature 303: 30–34, 1983
Holzmann B, McIntyre BW, Weissman IL: Identification of a murine Peyer's patch-specific lymphocyte homing receptor as an intergrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell 56: 37–47, 1989
Osborn L, Hession C, Tizard R, Vasallo C, Luhowskyj S, Ch-Rosso G, Lobb R: Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59: 1203–1211, 1989
Marlin SD, Springer TA: Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 51: 813–819, 1987
Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA: Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52: 925–933, 1988
Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR: VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60: 577–584, 1990
Dustin ML, Springer TA: Lymphocyte-function-associated antigen (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 107: 321–331, 1988
Rojkind M, Gatmaitan Z, Mackensen S, Gimbrone MA, Ponce P, Reid LM: Connective tissue biomatrix: its isolation and utilization for long-term cultures of normal rat hepatocytes. J Cell Biol 87: 255–263, 1980
Pauli BU, Lee CL: Inhibition of preference of adhesion between metastatic tumor cells and organ-specifically modulated endothelial cells. J Cell Biol 107: 45a, 1989
Johnson RC, Augustin-Voss HG, Pauli BU: Preferential binding of lung metastatic tumor cells to lung-derived endothelial cell surface vesicles. FASEB J 4: A1134, 1990
Rosen SD, Singer MS, Yednock TA: Involvement of sialic acid on endothelial cells in organ-specific lymphocyte recirculation. Science 228: 1005–1007, 1985
Rosen SD, Chi S, True DD, Singer MS, Yednock TA: Intravenously injected sialidase inactivates attachment sites for lymphocytes on high endothelial venules. J Immunol 142: 1895–1902, 1989
Yednock TA, Rosen SD: Lymphocyte homing. Adv Immunol 44: 313–378, 1989
Stoolman LM, Rosen SD: Possible role for cell-surface carbohydrate-binding molecules in lymphocyte recirculation. J Cell Biol 96: 722–729, 1983
Hammer DA, Lauffenburger DA: A dynamical model for receptor-mediated cell adhesion to surfaces. Biophys J 52: 475–487, 1987
Schmid-Schönbein GW, Fung YC, Zweifach BE: Vascular endothelium-leukocyte interactions: sticking shear force in venules. Circ Res 36: 173–185, 1975
Harlan JM: Leucocyte-endothelial interactions. Blood 65: 513–525, 1985
Lauffenburger DA, Hammer D, Tranquillo RT, Buettner H, Fisher E: How immune cells find their targets: quantitative studies of cell adhesion, migration and chemotaxis. In: Perelson AS (ed) Theoretical Immunology, Part Two, SFI Studies in the Sciences of Complexity. Addison-Wesley Publishing Company, 1988, pp 3–18
Chin YH, Rasmussen R, Cakiroglu AG, Woodruff JJ: Lymphocyte recognition of lymph node high endothelium. VI. Evidence of distinct structures mediating binding to high endothelial cells of lymph nodes and Peyer's patches. J Immunol 133: 2961–2965, 1984
Chin YH, Carey GP, Woodruff JJ; Lymphocyte recognition of lymp node high endothelium. IV. Cell surface structures mediating entry into lymph nodes. J Immunol 129: 1911–1915, 1982
Butcher E, Scollay R, Weissman I: Organ specificity of lymphocyte migration: Mediation by highly selective lymphocyte interaction with organ specific determinants on high endothelial venules. Eur J Immunol 10: 556–561, 1980
Goldsmith HL, Karino T: Physical and mathematical models of blood flow: Experimental studies. In: Meiselman HJ, Lichtman MA, LaCelle PL (eds) Erythrocyte Mechanics and Blood Flow. Alan R. Liss, Inc., 1980, pp 165–194.
Bell GI: Models for the specific adhesion of cells to cells. Science 200: 618–627, 1978
Goldman AJ, Cox RG, Brenner H: Slow viscous motion of a sphere parallel to a plane wall. II. Couette Flow. Chem Eng Sci 22: 653–659, 1967
Evans EA: Manuscript in preparation and personal correspondence (1990)
Hammer DA, Lauffenburger DA: A dynamical model for receptor-mediated cell adhesion to surfaces in viscous shear flow. Cell Biophys 14: 139–173, 1989
Yeung A, Evans EA: Cortical shell-liquid core model for passive flow of liquid-like spherical cells into micropipets. Biophys J 56: 139–149, 1989
Evans EA, Yeung A: Apparent viscosity and cortical tension of blood granulocytes determined by micropiper aspiration. Biophys J 56: 151–160, 1989
Schmid-Schönbein GW, Sung KLP, Tozeren H, Skalak R, Chien S: Passive mechanical properties of human leukocytes. Biophys J 36: 243–256, 1981
Weiss L, Schmid-Schönbein GW: Biomechanical interactions of cancer cells with the microvasculature during metastasis. Cell Biophys 14: 187–215, 1989
Hubbe MA: Adhesion and detachment of biological cellsin vitro. Prog Surg Sci 11: 65–137, 1981
Forrester JV, Lackie JM: Adhesion of neutrophils under conditions of flow. J Cell Sci 70: 93–110, 1984
Hammer DA: An analysis of receptor-mediated cell adhesion under conditions of flow. PhD Thesis, University of Pennsylvania, 1987
Lawrence MB, Smith CW, Eskin SG, McIntire IV: Effect of venous shear stress on CD18-mediated neutrophil adhesion to cultured endothelium. Blood 75: 227–237, 1990
Doroszewski J: Short term and incomplete cell-substrate adhesion. In: Curtis ASG, Pitts JD (eds) Cell Adhesion and Motility. Cambridge University Press, 1980, pp 171–197
Kishimoto TK, Jutila NA, Berg EL, Butcher EC: Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science 245: 1238–1241, 1989
Kramer RH, Gonzales R, Nicolson GL: Metastatic tumor cells adhere preferentially to the extracellular matrix underlying vascular endothelial cells. Int J Cancer 26: 639–645, 1980
Vlodavsky I, Fuks Z, Bar-Ner M, Ariav Y, Schirrmacher V: Lymphoma cell-mediated degradation of sulfated proteoglycans in the subendothelial extracellular matrix: relationship to tumor cell metastasis. Cancer Res 43: 2704–2711, 1983
Nakajima M, Irimura T, DiFerrante D, DiFerrante N, Nicolson GL: Heparan sulfate degradation: relation to tumor invasive and metastatic properties of mouse B16 melanoma sublines. Science 220: 611–613, 1983
Liotta LA, Rao CW, Wewer UM: Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem 55: 1037–1057, 1986
Nakajima M, Irimura T, Nicolson GL: Heparanases and tumor metastasis. J Cell Biochem 36: 157–167, 1988
Pauli BU, Knudsen W: Tumor invasion: a consequence of destructive and compositional matrix alteractions. Human Pathol 19: 628–639, 1988
Zucker S, Wieman J, Lysik RM, Imhof B, Nagase H, Ramamurthy N, Liotta LA, Golub LM: Gelatin-degrading type IV collagenase isolated from human small cell lung cancer. Invasion Metastasis 9: 167–181, 1989
Zimmerman A, Keller HU: Locomotion of tumor cells as an element of invasion and metastasis. Biomed Pharmacother 41: 337–344, 1987
Lapis K, Paku S, Liotta LA: Endothelialization of embolized tumor cells during metastasis formation. Clin Expl Metastasis 6: 73–89, 1988
Honn KV, Grossi IM, Diglio CA, Wojtukiewicz M, Taylor JD: Enhanced tumor cell adhesion to the subendothelial matrix resulting from 12(S)HETE-induced endothelial cell retraction. FASEB J 3: 2285–2293, 1989
Honn KV, Grossi IM, Chopra H, Steinert BW, Onoda J, Nelson KK, Taylor JD: Role of tumor cell eicosanoids and membrane glycoproteins IRGpIb and IRGpIIb/IIIa in metastasis. In: Nigam S, McBrien DCH, Slater TG (eds) Eicosanoids, Lipid Peroxiation and Cancer, Springer-Verlag, Berlin, 1988, pp 29–42
Grossi IM, Fitzgerald LA, Umbarger LA, Nelson KK, Diglio CA, Taylor JD, Honn KV: Bidirectional control of membrane expression and/or activation of tumor cell IRGIIb/IIIa receptor and tumor cell adhesion by lipoxygenase products of arachidonic acid and linoleic acid. Cancer Res 49: 1029–1037, 1989
El-Sabban ME, Pauli BU: Metabolic coupling between metastatic tumor cells and vascular endothelium. FASEB J 4: A911, 1990
Chopra H, Marzouq L, Taylor JD, Honn KV: Lipoxygenase product 12(S)HETE alters the organization of the tumor cell cytoskeleton and modulates integrin receptor function. Proc Am Assoc Cancer Res 30: 88, 1989
Hynes RO: Integrins: a family of cell surface receptors. Cell 48: 549–554, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pauli, B.U., Augustin-Voss, H.G., El-Sabban, M.E. et al. Organ-preference of metastasis. Cancer Metast Rev 9, 175–189 (1990). https://doi.org/10.1007/BF00046359
Issue Date:
DOI: https://doi.org/10.1007/BF00046359