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Metastatic Spread from Abdominal Tumor Cells to Parathymic Lymph Nodes

Pathology & Oncology Research volume 25, pages 625–633 (2019)Cite this article

Abstract

Metastatic studies on rats showed that after subrenal implantation of tumor cells under the capsule of the kidney or subhepatic implantation under Glisson’s capsule of the liver generated primary tumors in these organs. It was assumed that tumor cells that escaped through the disrupted peripheral blood vessels of primary tumors entered the peritoneal cavity, crossed the diaphragm, and appeared in the thoracal, primarily in the parathymic lymph nodes. This explanation did not answer the question whether distant lymph nodes were reached via the blood stream from the primary tumor or through the thoracal lymphatic vessels. In this work, we investigated the metastatic pathway in C3H/HeJ mice, after direct intraperitoneal administration of murine SCC VII cells bypassing the hematogenic spread of tumor cells. The direct pathway was also mimicked by intraperitoneal injection of Pelican Ink colloidal particles, which appeared in the parathymic lymph nodes, similarly to the tumor cells that caused metastasis in the parathymic lymph nodes and in the thymic tissue. The murine peritoneal-parathymic lymph node route indicates a general mechanism of tumor progression from the abdominal effusion. This pathway starts with the growth of abdominal tumors, continues as thoracal metastasis in parathymic lymph nodes and may proceed as mammary lymph node metastasis.

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References

  1. Trencsenyi G, Kertai P, Somogyi C, Nagy G, Dombradi Z, Gacsi M, Banfalvi G (2007) Chemically induced carcinogenesis affecting chromatin structure in rat hepatocarcinoma cells. DNA Cell Biol 26:649–655 http://online.liebertpub.com/doi/abs/10.1089/dna.2007.0587

    Article  CAS  PubMed  Google Scholar 

  2. Trencsenyi G, Kertai P, Bako F, Hunyadi J, Marian T, Hargitai Z, Pocsi I, Muranyi E, Hornyak L, Banfalvi G (2009) Renal capsule-Parathymic lymph node complex: a new in vivo metastatic model in rats. Anticancer Res 29:2121–2126 http://ar.iiarjournals.org/content/29/6/2121.long

    PubMed  Google Scholar 

  3. Cui ZY, Ahn JS, Lee JY, Kim WS, Lim HY, Jeon HJ, Suh SW, Kim JH, Kong WH, Kang JM, Nam DH, Park K (2006) Mouse orthotopic lung cancer model induced by PC14PE6. Cancer Res Treat 38:234–239 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741646/

    Article  PubMed  PubMed Central  Google Scholar 

  4. Paget S (1989) The distribution of secondary growths in cancer of the breast. Lancet 133(3421):571–573 https://www.ncbi.nlm.nih.gov/pubmed/2673568

    Article  Google Scholar 

  5. Hoffman RM (1999) Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Investig New Drugs 17:343–359 https://www.ncbi.nlm.nih.gov/pubmed?term=orthotopic%20metastatic%20mouse%20model%20for%20anticancer%20drug%20discovery%20and%20evaluation%20a%20bridge%20to%20the%20clinic.&cmd=correctspelling

    Article  CAS  Google Scholar 

  6. Rozsa D, Trencsenyi G, Kertai P, Marian T, Nagy G, Banfalvi G (2009) Lymphatic spread of mesenchymal renal tumor to metastatic parathymic lymph nodes in rat. Histol Histopathol 24:1367–1379 http://www.hh.um.es/Abstracts/Vol_24/24_11/24_11_1367.htm

    PubMed  Google Scholar 

  7. Marco AJ, Domingo M, Ruberte J, Carretero A, Briones V, Dominguez L (1992) Lymphatic drainage of Listeria inonocytogenes and Indian ink inoculated in the peritoneal cavity of the mouse. Lab Anim 26:200–205 http://journals.sagepub.com/doi/abs/10.1258/002367792780740549?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&

    Article  CAS  PubMed  Google Scholar 

  8. Banfalvi G (2012a) Role of parathymic lymph nodes in metastatic tumor development. Cancer Metastasis Rev 31:89–97 https://link.springer.com/article/10.1007%2Fs10555-011-9331-y

    Article  PubMed  Google Scholar 

  9. Steer HW, Lewis DA (1983) Peritoneal cell responses to acute gastro-intestinal inflammation. J Pathol 140:237–253 http://onlinelibrary.wiley.com/doi/10.1002/path.1711400306/full

    Article  CAS  PubMed  Google Scholar 

  10. Jian J, Liu C, Gong Y, Su L, Zhang B, Wang Z, Wang D, Zhou Y, Xu F, Li P, Zheng Y, Song L, Zhou X (2014) India ink incorporated multifunctional phase-transition Nanodroplets for photoacoustic/ultrasound dual-modality imaging and photoacoustic effect based tumor therapy. Theranostics 4(10):1026–1038 http://www.thno.org/v04p1026.htm

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rafferty P, Egenolf D, Brosnan K, Makropoulos D, Jordan J, Meshaw K, Walker M, Volk A, Bugelski PJ (2012) Immunotoxicologic effects of cyclosporine on tumor progression in models of squamous cell carcinoma and B-cell lymphoma in C3H mice. J Immunotoxicol 9:43–55 http://www.tandfonline.com/doi/full/10.3109/1547691X.2011.614646

    Article  CAS  PubMed  Google Scholar 

  12. Moore A, Sergeyev N, Bredow S, Weissleder R (1998) A model system to quantitate tumor burden in locoregional lymph nodes during cancer spread. Invasion Metastasis 18:192–197 https://www.ncbi.nlm.nih.gov/pubmed/10640905

    Article  PubMed  Google Scholar 

  13. Morris B, Courtice FC (1977) Cells and immunoglobulins in lymph. Lymphology 10:62–69 https://www.ncbi.nlm.nih.gov/pubmed/329011

    CAS  PubMed  Google Scholar 

  14. Miller JF (1963) Role of the thymus in immunity. Brit Med J 24 2(5355):459–464. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874012/

    Article  CAS  Google Scholar 

  15. Bonney WM, Battenberg JD (1967) Transthoracic thymectomy in rats. Transplantation 5(3):544–546. https://www.ncbi.nlm.nih.gov/pubmed/?term=Bonney+WM%2C+Battenberg+JD.+Transthoracic+thymectomy+in+rats

    Article  CAS  PubMed  Google Scholar 

  16. Blau JN, Gaugas JM (1968) Parathymic lymph nodes in rats and mice. Immunology 14:763–765 https://www.ncbi.nlm.nih.gov/pubmed/?term=Blau+JN%2C+Gaugas+JM.+Parathymic+lymph+nodes+in+rats+and+mice

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Tanegashima A, Yamashita A, Yamamoto H, Fukunaga T (1999) Human parathymic lymph node: morphological and functional significance. Immunology 97(2):301–308 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2326821/

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Severeanu G (1909) Die Lymphgefäße der Thymus. Arch Anat Entw Gesch 93

  19. Siegler R (1669-1678) Rich MA (1963) unilateral histogenesis of AKR thymic lymphoma. Cancer Res Volume 23:10(1) http://cancerres.aacrjournals.org/content/23/10_Part_1/1669.long

  20. Workman P, Twentyman P, Balkwill F (1988) United Kingdom co-ordinating committee on Cancer research (UKCCCR) guidelines for the welfare of animals in experimental neoplasia (second edition). Br J Cancer 77(1):1–10 https://ciepal-azur.unice.fr/Oncology%20animal%20guides.pdf

    Google Scholar 

  21. Kanazawa H, Rapacchietta D, Kallman RF (1988) Schedule-dependent therapeutic gain from the combination of fractionated irradiation and cis-diamminedichloroplatinum (II) in C3H/km mouse model systems. Cancer Res 48:3158–3164 http://cancerres.aacrjournals.org/content/48/11/3158.short

    CAS  PubMed  Google Scholar 

  22. Dunn TB (1954) Normal and pathologic anatomy of the reticular tissue in laboratory mice, with a classification and discussion of neoplasms. J Natl Cancer Inst 14(6):1281–1433 https://www.ncbi.nlm.nih.gov/pubmed/13233863

    CAS  PubMed  Google Scholar 

  23. Glomset DA (1938) The incidence of metastasis of malignant tumors to the adrenals. Am J Cancer 32:57–61 http://cancerres.aacrjournals.org/content/amjcancer/32/1/57.full.pdf

    Article  Google Scholar 

  24. Trencsenyi G, Marian T, Bako F, Emri M, Nagy G, Kertai P, Banfalvi G (2014a) Metastatic hepatocarcinoma he/De tumor model in rat. J Cancer 5(7):548–558. https://doi.org/10.7150/jca.9315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Trencsenyi G, Nagy G, Kahlik B, Nemeth E, Kertai P, Kiss A, Banfalvi G (2014b) Lymphoid metastasis of rat My2/De leukemia. Leuk Res 38:586–593. https://doi.org/10.1016/j.leukres.2014.02.006

    Article  CAS  PubMed  Google Scholar 

  26. Pitt ML, Anderson AO (1988) Direct transdiaphragmatic traffic of peritoneal macrophages to the lung. Adv Exp Med Biol 237:627–632 https://link.springer.com/chapter/10.1007/978-1-4684-5535-9_95

    Article  CAS  PubMed  Google Scholar 

  27. MacCallum WG (1903) On the mechanism of absorption of granular materials from the peritoneum. Bull Johns Hopkins Hosp 14:105–115

    Google Scholar 

  28. Olin T, Saldeen T (1964) The lymphatic pathways from the peritoneal cavity: a lymphangiographic study in the rat. Cancer Res 24:1700–1711 http://cancerres.aacrjournals.org/content/24/10/1700.long

    CAS  PubMed  Google Scholar 

  29. Banfalvi G (2012b) Metastatic view of breast cancer. Cancer Metastasis Rev 31:815–822. https://doi.org/10.1007/s10555-012-9392-6

    Article  CAS  PubMed  Google Scholar 

  30. Gray H, Pickering PT, Howden R (1974) Gray’s anatomy. Philadelphia Courage Books

  31. Handley RS, Thackray AC (1954) Invasion of the internal mammary glands in carcinoma of the breast. Br J Cancer 1:15–20

    Article  Google Scholar 

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Acknowledgements

The SCC VII tumor cell line was kindly provided by Prof. Reinhard Zeidler, University of Munich, Helmholtz Zentrum. The research was supported by the EU and co-financed by the European Regional Development Fund under the GINOP-2.3.2-15-2016-00005 to IJ.

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Author notes

  1. István Juhász and Gáspár Bánfalvi contributed equally to this work.

Authors and Affiliations

  1. Department of Biotechnology and Microbiology, University of Debrecen, 1 Egyetem Square, Debrecen, 4010, Hungary

    Gábor Király, Gábor Szemán-Nagy & Gáspár Bánfalvi

  2. Department of Surgery and Operative Techniques, University of Debrecen, 98 Nagyerdei körút, Debrecen, 4012, Hungary

    Gábor Király & István Juhász

  3. Department of Pathology, Kenézy Hospital, University of Debrecen, 2-28 Bartok Street, Debrecen, 4031, Hungary

    Zoltán Hargitai & Ilona Kovács

  4. Department of Dermatology, University of Debrecen, 98 Nagyerdei körút, Debrecen, 4012, Hungary

    István Juhász

Authors
  1. Gábor Király
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  2. Zoltán Hargitai
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  3. Ilona Kovács
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  4. Gábor Szemán-Nagy
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  5. István Juhász
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  6. Gáspár Bánfalvi
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Contributions

Conception and design: G. Banfalvi, G. Kiraly, G. Nagy, I. Juhasz.

Collection and assembly of data: G. Kiraly, G. Nagy, Z. Hargitai, I. Kovacs.

Data analysis and interpretation: G. Banfalvi, G. Kiraly, G. Nagy, I. Juhasz.

Manuscript writing: G. Banfalvi, G. Kiraly, G. Nagy, I. Juhasz.

Final approval of manuscript: I. Juhasz, G. Banfalvi, G. Nagy.

Accountable for all aspects of the work: G. Banfalvi, I. Juhasz, G. Nagy.

Corresponding authors

Correspondence to István Juhász or Gáspár Bánfalvi.

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Király, G., Hargitai, Z., Kovács, I. et al. Metastatic Spread from Abdominal Tumor Cells to Parathymic Lymph Nodes. Pathol. Oncol. Res. 25, 625–633 (2019). https://doi.org/10.1007/s12253-018-0492-7

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  • DOI: https://doi.org/10.1007/s12253-018-0492-7

Keywords

  • Carcinoma cell line
  • Murine metastasis model
  • Parathymic lymph node
  • Colloidal ink