Abstract
The metastatic spread of tumors is not a random process. Distinct patterns of metastasis can be discerned which vary from tumor type to tumor type. A common pattern, particularly for carcinomas, is that regional lymph nodes are often the first organs to develop metastases. This pattern of metastasis is central to the utility of the sentinellymphonodectomy surgical technique. However, not all tumors and tumor types metastasize first to the regional lymph nodes. The mechanisms which determine whether regional lymph nodes or other sites first develop metastases remain poorly understood. In this article I review the anatomical, cellular and molecular factors which play a role in metastatic dissemination and determine patterns of metastasis. I then explore the importance of tumor heterogeneity and the selection of metastatically competent tumor cells during systemic dissemination, and suggest that some secondary sites are more readily colonised by metastasizing cells than others. Metastases at these sites act as bridgeheads, constituting a reservoir of tumor cells which, because they have already successfully metastasized, possess many of the properties required for metastasis to further sites. These tumor cells are therefore more likely than cells in the primary tumor to acquire all of the properties required for metastasis to less favourable secondary sites. To illustrate the bridgehead concept, I argue that features of the design and function of the lymphatic system make it highly amenable to the entry of metastasizing tumor cells and the formation of lymph node metastases, and suggest that lymph node metastases form a bridgehead for further metastatic spread.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Aaronson, S. (1991). Growth factors and cancer. Science 254: 1146–1153
Achen, M., Jeltsch, M., Kukk, E., Makinen, T., Vitali, A., Wilks, A., Alitalo, K. and Stacker, S. (1998). Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3. Proc. Natl.. Acad. Sci USA 95: 548–553
Amundson, S., Myers, T. and Pomace, A. (1998). Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress. Oncogene 17: 3287–3299
Aukland, K. and Reed, R. (1993). Interstitial-Lymphatic mechanisms in the control of extracellular fluid volume. Physiological Reviews 73: 1–75
Bates, R., Lincz, L. and Burns, G. (1995). Involvement of integrins in cell survival. Cancer Metastasis Rev. 14: 191–203
Beahrs, O. and Myers, M. (1983). Purposes and priciples of staging. Manual for staging of cancer p3–5. J. B. Lippincott Co., Philadelphia
Birchmeier, W. and Behrens, J. (1984). Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1198: 11–26
Brodt, P. (1991). Adhesion mechanisms in lymphatic metastasis. Cancer Metastasis Rev. 10: 23–32
Butler, T. and Gullino, P. (1975). Quantitation of cell shedding into efferent blood of mammary carcinoma. Cancer Research 35: 512–516
Cabanas, R. (1977). An approach for the treatment of penile carcinoma. Cancer 39: 456–466
Carr, I. (1983). Lymphatic metastasis. Cancer Metastasis Rev. 2: 307–317
Chambers, A., Macdonald, I., Schmidt, E., Koop, S., Morris, V., Khoka, R. and Groom, A. (1995). Steps in tumor metastasis: new concepts from intravital videomicroscopy. Cancer and Metastasis Reviews 14: 279–301
Chan, B., Matsuura, N., Takada, Y., Zetter, B. and Hemler, M. (1991). In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science 251: 1600–1602
Denko, N., Giaccia, A., Stringer, J. and Stambrook, P. (1994). The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle. Proc. Natl.. Acad. Sci. USA 91: 5124–5128
Deutsch, A., Lubach, D., Nissen, S. and Neukam, D. (1992). Ultrastructural studies on the invasion of melanomas in initial lymphatics of human skin. J. Invest Dermatol. 98: 64-67
de Waal, R., van Altena, M., Erhard, H., Weidle, U., Nooijen, P. and Ruiter D. (1997). Lack of lymphangiogenesis in human primary cutaneous melanoma. Am. J. Pathol. 150: 1951–1957
Duffy, M. (1992). The role of proteolytic enzymes in cancer invasion and metastasis. Cin. Exp. Metastasis 10: 1455–155
Dvorak, H. (1986). Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 315:1650–1659
Ennis, R., Katz, A., de Vries, G., Heitjan, D., O’Toole, K., Rubin, M., Buttyan R., Benson, M. and Schiff, P. (1997). Detection of circulating prostate carcinoma cells via an enhanced reverse transcriptase-polymerase chain reaction assay in patients with early stage prostate carcinoma. Independence from other pretreatment characteristics. Cancer 79: 2402–2408
Ewing, J. (1928). Metastasis. In: Neoplastic disease, a treatise on tumors. 3rd edition, Saunders, Philadelphia
Fallowfield, M. and Cook, M. (1990). Lymphatics in primary cutaneous melanoma. Am J. Surg. Pathol. 14: 370–374
Fearon, E. and Vogelstein, B. (1990). A genetic model for colorectal tumorigenesis. Cell 61: 759–767
Fidler, I. (1970). Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125I_5_iodo_2’-deoxyuridine. J. Natl.. Cancer Inst. 45: 773–782
Fidler, I. (1978). Tumor heterogeneity and the biology of cancer invasion and metastasis. Cancer research 38: 2651–2660
Fisher, B and Fisher, E. (1966). The interrelationship of hematogenous and lymphatic tumor cell dissemination. Surg. Gynecol. Obstet. 122: 791–798
Fisher, B and Fisher, E. (1970). Significance of the interrelationship of the lymph and blood vascular systems in tumor cell dissemination. Prog. Clin. Cancer 4: 84–96
Pitz, L., Morris, J., Towler, P., Long, A., Burgess, P., Greco, R., Wang, J., Gassaway, R., Nickbarg, E., Kovacic, S., Ciarletta, A., Giannotti, J., Finnerty, H., Zollner, R., Beier, D., Leak, L., Turner, K. and Wood, C. (1997). Characterisation of murine Flt4 ligand/VEGF-C. Oncogene 15: 613–618
Foulds, L. (1975). Neoplastic development. Academic Press, New York
Goldman, E. (1906). Relation of cancer cells to blood vessels and ducts. Lancet 1: 23
Gomez, D., Alonso, D., Yoshiji, H. and Thorgeirsson, U. (1997). Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur. J. Cell Biol, 74: 111–122
Grundmann, E. and Vollmer, E. (1985). Early local reaction and lymph node permeation of rat carcinoma HH9-cl 14 cells. An immunohistological approach. Pathol Res Pract 179: 304–309
Gualberto, A., Aldape, K., Kozakiewicz, K. and Tlsty, T. (1998). An oncogenic form of p53 confers a dominant gain-of-function phenotype that disrupts spindle checkpoint control. Proc. Natl.. Acad. Sci. USA 95: 5166–5171
Gulec, S., Moffat, E, Carroll, R., Serafini, A., Skakianakis, G., Aile, L., Boggs, J., Escobedo, D., Pruett, C; Gupta, A., Livingstone, A. and Krag, D. (1998). Sentinel lymph node localization in early breast cancer. J. Nuclear Med. 39: 1388–1393
Guyton, A. and Hall, A. (1996). Textbook of Medical Physiology (9th ed.). W. B. Saunders Company, Philadelphia, USA
Hanahan, D. and Folkman, J. (1996). Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86: 353–364
Harveit, E (1990). Attenuated cells of the breast stroma: the missing lymphatic system of the breast. Histopathology 16: 533–543
Heiss, M., Allgayer, H., Gruetzner, K., Funke, I., Babic, R., Jauch, K.-W. and Schildberg, E (1995). Individual development and uPA-receptor expression of disseminated tumor cells in bone marrow: a reference to early systemic disease in solid cancer. Nature Med. 1: 1035–1039
Hesketh, J., Vasconcelos, M. and Bermano, G. (1998). Regulatory signals in messenger RNA: determinants of nutrient-gene interaction and metabolic compartmentation. Br. J. Nutr. 80: 307–321
Hill, R., Chambers, A., Ling, V. and Harri S.J. (1984). Dynamic heterogeneity: rapid generation of metastatic varinats of mouse B16 melanoma cells. Science 224: 998–1001
Hockenberry, D., Nunez, G., Milliman, C., Screiber, R. and Korsmeyer, S. (1990). Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334–336
Hollstein, M., Sidransky, D., Vogelstein, B. and Harris, C. (1991). p53 mutations in human cancers. Science 253: 49–53
Honn, K. and Tang, D. (1992). Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix. Cancer and Metastasis Reviews 11: 353–375
Imhof, B., Piali, L., Gisler, R. and Dunon, D. (1996). Involvement of a6 and av integrins in metastasis. Current Topics in Microbiology and Immunology 213/1: 195–203
Israeli, R., Miller, W., Su, S., Powell, C., Fair, W., Samadi, D., Huryk, R., DeBlasio, A., Edwards, E., Wise, G. et al. (1994). Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison of prostate-specific membrane antigen and prostate-specific antigen-based assays. Cancer Research 54: 6306–6310
Jain, R. (1989). Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. J. Natl.. Cancer Inst. 81: 52–58
Jeltsch, M., Kaipainen, A., Joukov, V., Meng, X., Lakso, M., Rauvala, H., Swartz, M., Fukumura, D., Kain, R. and Alitalo, K. (1997). Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 276: 1423–1425
Joukov, V., Pajusola, K., Kaipainen, A., Chilov, D., Lahtinen, I., Kukk, E., Saksela, O., Kalkkinen, N. and Alitalo, K. (1996). A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 15: 290–298
Jussila, L., Valtola, R., Partanen, T., Salven, P., Heikkila, P., Matikainen, M.-T., Renkonen, R., Kaipainen, A., Detmar, M., Tschachler, E., Alitalo, R. and Alitalo, K. (1998). Lymphatic endothelium and Kaposi’s sarcoma spindle cells detected by antibodies against the vascular endothelial growth growth factor receptor-3. Cancer Res. 58: 1599–1604
Kaipainen, A., Korhonen, J., Mustonen, T., van Hinsberg, V., Fang, G.-H., Dumont, D., Breitman, M. and Alitalo, K. (1995). Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc. Natl. Acad. Sci. USA 92: 3566–3570
Karin, M. (1992). Signal transduction from cell surface to nucleus in development and disease. FASEB J. 6: 2581–2590
Kebers, F., Lewalle, J.-M., Desreux, J., Munaut, C; Devy, L., Foidart, J.-M., Noel, A. (1998). Induction of endothelial cell apoptosis by solid tumor cells. Exp. Cell Res 240: 197–205
Kerbel, R., Waghorne, C. and Korczak, B. (1988). Clonal dominance of primary tumours by metastatic cells: genetic analysis and biological implications. Cancer Surv. 7: 597–629
Kim, U. and Furth, J. (1960). Relation of mammotropes to mammary tumors. IV. Development of highly hormone-dependent mammary tumors. Proc. Soc. Exptl. Biol. Med. 105: 490–492
Kim, J., Yu, W., Kovalski, K. and Ossowski, L. (1998). Requirement for specific proteases in cancer cell intravasation as revealed by a novel semiquantitative PCR-based assay. Cell 94: 353–362
Knudson, A. (1993). Antioncogenes and cancer. Proc. Natl. Acad. Sci. USA 90: 10914–10921
Koch, F. E. (1939). Zur Frage der Metastasenbildung bei Impftumoren. Z. Krebsforsch. 48: 495–507
Kulakowski, A., Madej, G. and Pienkowski, T. (1984). Distribution of lymph node metastases in the malignant melanoma of the trunk. Oncology 41: 242–244
Kukk, E., Lymboussaki, A., Taira, S., Kaipainen, A., Jeltsch, M., Joukov, V. and Alitalo, K. (1996). VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development 122: 3829–3837
Leak, L. and Burke, J. (1968). Ultrastructual studies on the lymphatic anchoring filaments. J. Cell Biol. 36: 129–149
Lee, E., Lee, W.-H., Kaetzel, C., Parry, G. and Bissel, M. (1985). Interaction of mouse mammary epithelial cells with collagen substrates: regulation of casein gene expression and secretion. Proc. Natl. Acad. Sci USA 82: 1419–1423
Lee, J., Gray, A., Yuan, J., Luoh, S.-M., Avraham, H. and Wood, W. (1996). Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc. Natl. Acad. Sci. USA 93: 1988–1992
Li, M., Aggeler, J., Farson, D., Hatier, C., Hussell, J. and Bissell, M. (1987). Influence of reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc. Natl. Acad. Sci. USA 84: 136–140
Liotta, L., Mandler, R., Murano, G., Katz, D., Gordon, R., Chiang, P. and Schiffman, E. (1986). Tumor-cell autocrine motility factor. Proc. Natl. Acad. Sci. USA 83: 3302–3306
Lubach, D., Berens von Rautenfeld, D. and Kaiser, H. (1992). The possible role of the initial lymph vessels of the skin during metastasis of malignant tumors. In vivo, 6: 443–450
Ludwig, J. and Titus J. (1967). Experimental tumor cell emboli in lymph nodes. Arch. Pathol. 84: 304–311
McCarthy, S., Kuzu, I., Gatter, K. and Bicknell, R. (1991). Heterogeneity of the endothelial cell and its role in organ preference of tumour metastasis. Trends Pharmacol Sci. 12: 462–467
McCormack, S., Weaver, Z., Deming, S., Natarajan, G., Torri, J., Johnson, M., Liyanage, M., Ried, T. and Dickson, R. (1998). Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and chromosomal instability. Oncogene 16: 2755–2766
Melchior, S., Corey, E., Ellis, W., Ross, A., Layton, T., Oswin, M., Lange, P. and Vessella, R. (1997). Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate. Clin. Cancer Res. 3: 249–256
Mori, M., Mimori, K., Ueo, H., Karimine, N., Barnard, G., Sugimachi, K. and Akiyoshi, T. (1996). Molecular detection of circulating solid carcinoma cells in the peripheral blood: the concept of early systemic disease. Int. J. Cancer 68: 739–743
Naik, P., Karrim, J. and Hanahan, D. (1996). The rise and fall of apoptosis during multistage tumorigenesis: down-modulation contributes to tumor progression from angiogenic progenitors. Genes Dev. 10: 2105–2116
Nicolson, G. (1982). Cancer Metastasis: organ colonisation and the cell-surface properties of malignant cells. Biochim. Biophy. Acta 695: 113–176
Nicolson, G. (1987). Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res. 47: 1473–1487
Nicolson, G. (1988). Organ specificity of tumor metatasis: role of preferential adhesion, invasion and growth of malignant cells at specific sites. Cancer and Metastasis Reviews 7: 143–188
Nicolson, G. (1991). Gene expression, cellular diversification and tumor progression to the metastatic phenotype. Bioessays 13: 337–342
Nicolson, G. and Poste, G. (1982). Tumor cell diversity and host response in cancer metastasis. Curr. Prob. Cancer 7: 1–83
Oh SJ, Jeltsch MM, Birkenhager R, McCarthy JE, Weich HA, Christ B, Alitalo K, Wilting J (1997). VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev, Biol. 188: 96–109
Padget, S. (1889). Distribution of secondary growths in cancer of the breast. Lancet 1: 571–573
Pauli, B., Augustin-Voss, H., El-Sabban, M., Johnson, R. and Hammer, D. (1990). Organ-preference of metastasis: the role of endothelial cell adhesion molecules. Cancer and Metastasis Reviews 9: 175–189
Pawelec, G., Zeuthen, J. and Kiessling, R. (1997). Escape from host-antitumor immunity. Crit. Rev. Oncog. 8: 111–141
Poste, G., Tzeng, J., Doll, J., Greig, R., Rieman, D. and Zeidman, I. (1982). Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases. Proc. Natl. Acad. Sci. USA 79: 6574–6578
Powell, W. and Matrisian, L. (1996). Complex roles of matrix metalloproteinases in tumor progression. Curr. Top. Microbiol. Immunol. 213/1: 1–21
Price, J., Aukerman, S. and Fidler, I. (1986). Evidence that the process of murine melanoma metastasis is sequential and selective and contains stochastic elements. Cancer Res. 46: 5172–5178
Rajotte, D., Arap, W., Hagedorn, M., Koivunen, E., Pasqualini, R. and Ruoslahti, E. (1999). Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. J. Clin. Invest. 102: 430–437
Ratcliffe, P., O’Rourke, J., Maxwell, P. and Pugh, C. (1998). Oxygen sensing, hypoxia-inducible factor-1 and the regulation of mammalial gene expression. J. Exp. Biol. 201: 1153–1162
Raz, A. and Ben-Ze’ev, A. (1983) Modulation of the metastatic capability in BI6 melanoma by cell shape. Science 221: 1307–1310
Reed, J. (1998). Bcl-2 family proteins. Oncogene 17: 3225–3236
Rosenberg, S. (1993). Principles and applications of biologic therapy. In Cancer, Principles and Practice of Oncology, Fourth Edition, Eds Devita, Hellman and Rosenberg, pp 293–324. J. B. Lippincott Co., Philadelphia
Ryan, T. (1987). Structure and function of lymphatics. J. Invest. Dermatol. 93: 18S–23 S
Salsbury, A. (1975). The significance of the circulating cancer cell. Cancer Treat. Rev. 2: 55–72
Sato, H., Khato, J., Sato, T. and Suzuki, M. (1977). Deformability and filtrability of tumor cells through “nucleopore” filter, with reference to viability and metastatic spread. Gann monogr. Cancer Res. 20: 3–13
Sato, H. and Suzuki, M. (1976). In Fundamental aspects of metastasis (Weiss, L., ed.), pp 311–317. North Holland Publishing Co., Amsterdam
Searle, P. and Young, L. (1996). Immunotherapy II: antigens, receptors and costimulation. Cancer Metastasis Rev. 15: 329–349
Shibata, M., Maroulakou, I., Jorcyk, C., Gold, L., Ward, J. and Green, J. (1996). p53-independent apoptosis during mammary tumor progression in C3(1)/SV40 large T transgenic mice: suppression of apoptosis during transition from preneoplasia to carcinoma. Cancer Res. 56: 2998–3003
Shimonaka, M. and Yamaguchi, Y. (1994). Purification and biological characterisation of epitaxin, a fibroblast-der ived motility factor for epithelial cells. J. BioL. Chem. 269: 14284–14289
Sugarbaker, E. (1979). Cancer metastasis: a product of tumor-host interactions. In Current Problems in Cancer, Vol. III, R. Hickey, Ed. YearBook Medical Publishers, Chicago
Sugarbaker, E. (I98I). Patterns of metastasis in human malignancies. Cancer Biol. Rev. 2: 235–278
Symonds, H., Krall, L., Remington, L., Saenz-Robles, M., Lowe, S., Jacks, T. and Van Dyke, T. (1994). p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 78: 703–711
Takaoka, A., Adachi, M., Okuda, H., Sato, S., Yawata, A., Hinoda, Y., Takayama, S., Reed, J. and Imai, K. (1997). Anti cell death activity promotes pulmonary metastasis of melanoma cells. Oncogene 14: 2971–2977
Taplin, M., Bubley, G., Shuster, T., Frantz, M., Spooner, A., Ogata, G., Keer, H. and Balk, S. (1995). Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N. Engl. J. Med. 332: 1393–1398
Tarin, D., Price, J., Kettlewell, M., Souter, R., Vass, A. and Crossley, B. (1984). Mechanisms of human metastasis studied in patients with peritovenous shunts. Cancer Res. 44: 3584–3592
Tlsty, D. (1998). Cell-adhesion-dependent influences on genomic instability and carcinogenesis. Current Opinion in Cell Biology 10: 647–653
Tsubura, E., Yamashita, T. and Sone, S. (1983). Inhibition of the arrest of hematogenously disseminated tumor cells. Cancer Metastasis Rev. 2: 223–237
Updyke, T. and Nicolson, G. (1986). Malignant melanoma cell lines selected in vitro for increased homotypic adhesion properties have increased experimental metastasis potential. Clin. Exp. Metastasis 4: 273–284
Viney, J. (1995). Transgenic and gene knockout mice in cancer research. Cancer Metastasis Rev. 14: 77–90
Walker, P., Saas, P. and Dietrich, P. (1997). Role of fas ligand (CD95L) in immune escape: the tumor cell strikes back. J. Immunol. 158: 4521–4524
Weinberg, R. (1995). The molecular basis of oncogenes and tumor suppressor genes. Ann. N. Y. Acad. Sci. 758: 331–338
Weinstein, I. B. (1988). The origins of human cancer: molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment-tenty seventh G. H. A. Clowes memorial award lecture. Cancer Res. 48: 4135–4143
Weinstock, M., Clark, J. and Calabresi, P. (1993). Melanoma. In Medical Oncology, 2nd edition (Eds. Calabresi and Schein), p 545–563. McGraw-Hill, Inc., New York, USA
Weiss, J. M., Sleeman, J. P., Renkl, A. C., Termeer, C., Dittmar, H., Taxis, S., Howells, N., Hofmann, M., Schopf, E., Ponta, H., Herrlich P. and Simon, J. C. (1997). An essential role for CD44 variant isoforms in epidermal Langerhans cell and blood dendritic cell function. J. Cell Biol. 137: 1137–1147
Weiss, L. (1983). Random and nonrandom processes in metastasis and metastatic efficiency. Invasion Metastasis 3: 193–208
Weiss, L. and Ward, P (1983). Cell detachment and metastasis. Cancer Metastasis Rev. 2: 111–127
Weitz, J., Kienle, P., Lacroix, J., Willeke, E, Benner, A., Lehnert, T., Herfarth, C. and von Knebel Doeberitz, M. (1998). Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin. Cancer Res. 4: 343–348
Willis, R. A. (1975). Metastasis via the lymphatics. In: The spread of tumours in the human body, third edition. Butterworths, London
Yin, X., Grove, L., Dataa, N., Long, M. and Prochownik, E. (1999). C-myc overexpression and p53 loss cooperate to promote genomic instability. Oncogene 18: 1177–1184
Yoshizawa, M., Shingaki, S., Nakajima, T. and Saku, T. (1994). Histopathological study of lymphatic invasion in squamous cell carcinoma (0-1 N) with high potential of lymph node metastasis. Clin. Exp. Metastasis 12: 347–356
Young, R., Perez, C. and Hoskins, W. (1993). Cancer of the ovary. In: Cancer, Principles and Practice of Oncology, Fourth Edition, Eds Devita, Hellman and Rosenberg, pp 1226–1263. J. B. Lippincott Co., Philadelphia
Zeidman, I. and Buss, J. (1952). Transpulmonary passage of tumor cell emboli. Cancer Res. 12: 731–733
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Sleeman, J.P. (2000). The Lymph Node as a Bridgehead in the Metastatic Dissemination of Tumors. In: Schlag, P.M., Veronesi, U. (eds) Lymphatic Metastasis and Sentinel Lymphonodectomy. Recent Results in Cancer Research, vol 157. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57151-0_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-57151-0_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-63070-5
Online ISBN: 978-3-642-57151-0
eBook Packages: Springer Book Archive