Metastatic Spread from Abdominal Tumor Cells to Parathymic Lymph Nodes
- 69 Downloads
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.
KeywordsCarcinoma cell line Murine metastasis model Parathymic lymph node Colloidal ink
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.
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.
- 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 CrossRefGoogle 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/ CrossRefGoogle 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 CrossRefGoogle 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 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& CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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/ CrossRefGoogle 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 CrossRefGoogle 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 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/ CrossRefGoogle Scholar
- 18.Severeanu G (1909) Die Lymphgefäße der Thymus. Arch Anat Entw Gesch 93Google Scholar
- 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 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 CrossRefGoogle 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 CrossRefGoogle Scholar
- 27.MacCallum WG (1903) On the mechanism of absorption of granular materials from the peritoneum. Bull Johns Hopkins Hosp 14:105–115Google 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 Google Scholar
- 30.Gray H, Pickering PT, Howden R (1974) Gray’s anatomy. Philadelphia Courage BooksGoogle Scholar