Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2010

01.10.2010 | Original Paper

Biphasic effect of a primary tumor on the growth of secondary tumor implants

verfasst von: Juan Bruzzo, Paula Chiarella, Roberto P. Meiss, Raúl A. Ruggiero

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2010

Einloggen, um Zugang zu erhalten

Abstract

Background

The phenomenon of hormesis is characterized by a biphasic dose–response, exhibiting opposite effects in the low- and high-dose zones. In this study, we explored the possibility that the hormesis concept may describe the interactions between two tumors implanted in a single mouse, such that the resulting tumors are of different sizes.

Materials and methods

We used two murine tumors of spontaneous origin and undetectable immunogenicity growing in BALB/c mice. A measure of cell proliferation was obtained by immunostaining for Ki-67 protein and by using the [3H] thymidine uptake assay. For serum fractionation, we utilized dialysis and chromatography on Sephadex G-15.

Results

The larger primary tumor induced inhibitory or stimulatory effects on the growth of the smaller secondary one, depending on the ratio between the mass of the larger tumor relative to that of the smaller one, with high ratios rendering inhibition and low ratios inducing stimulation of the secondary tumor.

Conclusion

Since metastases can be considered as natural secondary tumor implants in a tumor-bearing host and that they constitute the main problem in cancer pathology, the use of the concept of hormesis to describe those biphasic effects might have significant clinical implications. In effect, if the tumor-bearing host were placed in the inhibitory window, tumor extirpation could enhance the growth of distant metastases and, reciprocally, if placed in the stimulatory window, tumor extirpation would result not only in a reduction or elimination of primary tumor load but also in a slower growth or inhibition of metastases.
Literatur
Zurück zum Zitat Beecken WD, Engl T, Jonas D, Blaheta RA (2009) Expression of angiogenesis inhibitors in human bladder cancer may explain rapid metastatic progression after radical cystectomy. Int J Mol Med 23:261–266PubMed Beecken WD, Engl T, Jonas D, Blaheta RA (2009) Expression of angiogenesis inhibitors in human bladder cancer may explain rapid metastatic progression after radical cystectomy. Int J Mol Med 23:261–266PubMed
Zurück zum Zitat Bertin C, Weston LA, Huang T, Jander G, Owens T, Meinwald J, Schroeder FC (2007) Grass roots chemistry: meta-tyrosine, an herbicidal nonprotein amino acid. PNAS 104:16964–16969CrossRefPubMed Bertin C, Weston LA, Huang T, Jander G, Owens T, Meinwald J, Schroeder FC (2007) Grass roots chemistry: meta-tyrosine, an herbicidal nonprotein amino acid. PNAS 104:16964–16969CrossRefPubMed
Zurück zum Zitat Bonfil RD, Ruggiero RA, Bustuoabad OD, Meiss RP, Pasqualini CD (1988) Role of concomitant resistance in the development of murine lung metastases. Int J Cancer 41:415–422CrossRefPubMed Bonfil RD, Ruggiero RA, Bustuoabad OD, Meiss RP, Pasqualini CD (1988) Role of concomitant resistance in the development of murine lung metastases. Int J Cancer 41:415–422CrossRefPubMed
Zurück zum Zitat Calabrese EJ (2005) Historical blunders: how toxicology got the dose–response relationship half right. Cell Mol Biol (Noisy-le-grand) 51:643–654 Calabrese EJ (2005) Historical blunders: how toxicology got the dose–response relationship half right. Cell Mol Biol (Noisy-le-grand) 51:643–654
Zurück zum Zitat Calabrese EJ (2007) Cancer biology and hormesis: human tumor cell lines commonly display hormetic (biphasic) dose responses. Crit Rev Toxicol 35:463–582CrossRef Calabrese EJ (2007) Cancer biology and hormesis: human tumor cell lines commonly display hormetic (biphasic) dose responses. Crit Rev Toxicol 35:463–582CrossRef
Zurück zum Zitat Calabrese EJ (2008a) An assessment of anxiolytic drug screening tests: hormetic dose responses. Crit Rev Toxicol 38:489–542CrossRefPubMed Calabrese EJ (2008a) An assessment of anxiolytic drug screening tests: hormetic dose responses. Crit Rev Toxicol 38:489–542CrossRefPubMed
Zurück zum Zitat Calabrese EJ (2008b) Hormesis and medicine. BJCP 66:594–617 Calabrese EJ (2008b) Hormesis and medicine. BJCP 66:594–617
Zurück zum Zitat Chiarella P, Reffo V, Bruzzo J, Bustuoabad OD, Ruggiero RA (2008a) Therapeutic anti-tumor vaccines: from tumor inhibition to enhancement. Clin Med Oncol 2:1–9 Chiarella P, Reffo V, Bruzzo J, Bustuoabad OD, Ruggiero RA (2008a) Therapeutic anti-tumor vaccines: from tumor inhibition to enhancement. Clin Med Oncol 2:1–9
Zurück zum Zitat Chiarella P, Vulcano M, Bruzzo J, Vermeulen M, Vanzulli S, Maglioco A, Camerano GV, Palacios V, Fernández G, Fernández Brando R, Isturiz MA, Dran GI, Bustuoabad OD, Ruggiero RA (2008b) Anti-inflammatory pretreatment enables an efficient dendritic cell-based immunotherapy against established tumors. Cancer Immunol Immunother 57:701–718CrossRefPubMed Chiarella P, Vulcano M, Bruzzo J, Vermeulen M, Vanzulli S, Maglioco A, Camerano GV, Palacios V, Fernández G, Fernández Brando R, Isturiz MA, Dran GI, Bustuoabad OD, Ruggiero RA (2008b) Anti-inflammatory pretreatment enables an efficient dendritic cell-based immunotherapy against established tumors. Cancer Immunol Immunother 57:701–718CrossRefPubMed
Zurück zum Zitat Eichler O, Sies H, Stahl W (2002) Divergent optimum levels of lycopene, beta-carotene and lutein protecting against UVB irradiation in human fibroblasts. Photochem Photobiol 75:503–506CrossRefPubMed Eichler O, Sies H, Stahl W (2002) Divergent optimum levels of lycopene, beta-carotene and lutein protecting against UVB irradiation in human fibroblasts. Photochem Photobiol 75:503–506CrossRefPubMed
Zurück zum Zitat Farma JM, Pingpank JF, Libutti SK, Bartlett DL, Ohl S, Beresneva T, Alexander HR (2005) Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion. J Gastrointest Surg 9:1346–1353CrossRefPubMed Farma JM, Pingpank JF, Libutti SK, Bartlett DL, Ohl S, Beresneva T, Alexander HR (2005) Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion. J Gastrointest Surg 9:1346–1353CrossRefPubMed
Zurück zum Zitat Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–285CrossRefPubMed Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–285CrossRefPubMed
Zurück zum Zitat Franco M, Bustuoabad OD, di Gianni PD, Goldman A, Pasqualini CD, Ruggiero RA (1996) A serum-mediated mechanism for concomitant resistance shared by immunogenic and non-immunogenic tumours. Br J Cancer 74:178–186PubMed Franco M, Bustuoabad OD, di Gianni PD, Goldman A, Pasqualini CD, Ruggiero RA (1996) A serum-mediated mechanism for concomitant resistance shared by immunogenic and non-immunogenic tumours. Br J Cancer 74:178–186PubMed
Zurück zum Zitat Gao J, Wymore RS, Wang Y, Gaudette GR, Krukenkamp IB, Cohen IS, Mathias RT (2002) Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol 119:297–312CrossRefPubMed Gao J, Wymore RS, Wang Y, Gaudette GR, Krukenkamp IB, Cohen IS, Mathias RT (2002) Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol 119:297–312CrossRefPubMed
Zurück zum Zitat Honar H, Riazi K, Homayoun H, Sadeghispour H, Rashidi N, Ebrahimkhani MR, Mirazi N, Dehpour AR (2004) Ultra-low-dose naltrexone potentiates the anticonvulsant effect of low-dose morphine on clonic seizure. Neuroscience 129:733–742CrossRefPubMed Honar H, Riazi K, Homayoun H, Sadeghispour H, Rashidi N, Ebrahimkhani MR, Mirazi N, Dehpour AR (2004) Ultra-low-dose naltrexone potentiates the anticonvulsant effect of low-dose morphine on clonic seizure. Neuroscience 129:733–742CrossRefPubMed
Zurück zum Zitat Laird AK (1969) Dynamics of growth in tumors and in normal organisms. Natl Cancer Inst Monograph 30:15–28 Laird AK (1969) Dynamics of growth in tumors and in normal organisms. Natl Cancer Inst Monograph 30:15–28
Zurück zum Zitat Lange PH, Hekmat K, Bosl G, Kennedy BJ, Fraley EE (1980) Accelerated growth of testicular cancer after cytoreductive surgery. Cancer 45:1498–1506CrossRefPubMed Lange PH, Hekmat K, Bosl G, Kennedy BJ, Fraley EE (1980) Accelerated growth of testicular cancer after cytoreductive surgery. Cancer 45:1498–1506CrossRefPubMed
Zurück zum Zitat Loberg RD, Bradley DA, Tomlins SA, Chinnaiyan AM, Pienta KJ (2007) The lethal phenotype of cancer: the molecular basis of death due to malignancy. CA Cancer J Clin 57:225–241CrossRefPubMed Loberg RD, Bradley DA, Tomlins SA, Chinnaiyan AM, Pienta KJ (2007) The lethal phenotype of cancer: the molecular basis of death due to malignancy. CA Cancer J Clin 57:225–241CrossRefPubMed
Zurück zum Zitat McAllister SS, Gifford AM, Greiner AL, Kelleher SP, Saelzler MP, Ince TA, Reinhardt F, Harris LN, Hylander BL, Repasky EA, Weinberg RA (2008) Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell 133:994–1005CrossRefPubMed McAllister SS, Gifford AM, Greiner AL, Kelleher SP, Saelzler MP, Ince TA, Reinhardt F, Harris LN, Hylander BL, Repasky EA, Weinberg RA (2008) Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell 133:994–1005CrossRefPubMed
Zurück zum Zitat Meiss RP, Bonfil RD, Ruggiero RA, Pasqualini CD (1986) Histological aspects of concomitant resistance induced by nonimmunogenic murine tumors. J Natl Cancer Inst 76:1163–1175PubMed Meiss RP, Bonfil RD, Ruggiero RA, Pasqualini CD (1986) Histological aspects of concomitant resistance induced by nonimmunogenic murine tumors. J Natl Cancer Inst 76:1163–1175PubMed
Zurück zum Zitat Mimori K, Iwatsuki M, Yokobori T, Mori M (2009) Important matters to identify robust markers for metastasis and recurrence in solid cancer. Ann Surg Oncol 16:1070–1071CrossRefPubMed Mimori K, Iwatsuki M, Yokobori T, Mori M (2009) Important matters to identify robust markers for metastasis and recurrence in solid cancer. Ann Surg Oncol 16:1070–1071CrossRefPubMed
Zurück zum Zitat Norbury KC (1977) In vitro stimulation and inhibition of tumor cell growth mediated by different lymphoid cell populations. Cancer Res 37:1408–1415PubMed Norbury KC (1977) In vitro stimulation and inhibition of tumor cell growth mediated by different lymphoid cell populations. Cancer Res 37:1408–1415PubMed
Zurück zum Zitat O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315–328CrossRefPubMed O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315–328CrossRefPubMed
Zurück zum Zitat Prehn LM (1976) Immunostimulation of highly immunogenic target tumor cells by lymphoid cells in vitro. J Natl Cancer Inst 56:833–838PubMed Prehn LM (1976) Immunostimulation of highly immunogenic target tumor cells by lymphoid cells in vitro. J Natl Cancer Inst 56:833–838PubMed
Zurück zum Zitat Prehn RT (2006) The paradoxical effects of splenectomy on tumor growth. Theor Biol Med Model 3:6CrossRefPubMed Prehn RT (2006) The paradoxical effects of splenectomy on tumor growth. Theor Biol Med Model 3:6CrossRefPubMed
Zurück zum Zitat Prehn RT (2007) Immunostimulation and immunoinhibition of premalignant lesions. Theor Biol Med Model 4:6CrossRefPubMed Prehn RT (2007) Immunostimulation and immunoinhibition of premalignant lesions. Theor Biol Med Model 4:6CrossRefPubMed
Zurück zum Zitat Ruggiero RA, Bustuoabad OD, Bonfil RD, Meiss RP, Pasqualini CD (1985) “Concomitant immunity” in murine tumours of non-detectable immunogenicity. Br J Cancer 51:37–48PubMed Ruggiero RA, Bustuoabad OD, Bonfil RD, Meiss RP, Pasqualini CD (1985) “Concomitant immunity” in murine tumours of non-detectable immunogenicity. Br J Cancer 51:37–48PubMed
Zurück zum Zitat Ruggiero RA, Bustuoabad OD, Cramer P, Bonfil RD, Pasqualini CD (1990) Correlation between seric antitumor activity and concomitant resistance in mice bearing nonimmunogenic tumors. Cancer Res 50:7159–7165PubMed Ruggiero RA, Bustuoabad OD, Cramer P, Bonfil RD, Pasqualini CD (1990) Correlation between seric antitumor activity and concomitant resistance in mice bearing nonimmunogenic tumors. Cancer Res 50:7159–7165PubMed
Zurück zum Zitat Shearer WT, Parker CW (1978) Antibody and complement modulation of tumor cell growth in vitro and in vivo. Fed Proc 37:2385–2389PubMed Shearer WT, Parker CW (1978) Antibody and complement modulation of tumor cell growth in vitro and in vivo. Fed Proc 37:2385–2389PubMed
Zurück zum Zitat Southam CM (1968) Coexistence of allogeneic tumor growth and homograft immunity in man. Eur J Cancer 4:507–511PubMed Southam CM (1968) Coexistence of allogeneic tumor growth and homograft immunity in man. Eur J Cancer 4:507–511PubMed
Zurück zum Zitat Sugarbaker EV, Thornthwaite J, Ketcham AS (1977) Inhibitory effect of a primary tumor on metastases. In: Day SB et al (eds) Cancer invasion and metastasis. Biological mechanisms and therapy. Raven, New York, pp 227–240 Sugarbaker EV, Thornthwaite J, Ketcham AS (1977) Inhibitory effect of a primary tumor on metastases. In: Day SB et al (eds) Cancer invasion and metastasis. Biological mechanisms and therapy. Raven, New York, pp 227–240
Zurück zum Zitat Szabadi E (1977) Model of two functionally antagonistic receptor populations activated by the same agonist. J Theor Biol 69:101–112CrossRefPubMed Szabadi E (1977) Model of two functionally antagonistic receptor populations activated by the same agonist. J Theor Biol 69:101–112CrossRefPubMed
Zurück zum Zitat Thong HY, Maibath HI (2007) Hormesis [biological effects of low level exposure (BELLE)] and dermatology. Cutan Ocul Toxicol 26:329–341CrossRefPubMed Thong HY, Maibath HI (2007) Hormesis [biological effects of low level exposure (BELLE)] and dermatology. Cutan Ocul Toxicol 26:329–341CrossRefPubMed
Zurück zum Zitat Wise LE, Lichtman AH (2007) The uncompetitive N-methyl d-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task. Eur J Pharmacol 575:98–102CrossRefPubMed Wise LE, Lichtman AH (2007) The uncompetitive N-methyl d-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task. Eur J Pharmacol 575:98–102CrossRefPubMed
Zurück zum Zitat Zahalka MA, Okon E, Naor D (1993) Blocking lymphoma invasiveness with a monoclonal antibody directed against the beta-chain of the leukocyte adhesion molecule (CD18). J Immunol 150(10):4466–4477PubMed Zahalka MA, Okon E, Naor D (1993) Blocking lymphoma invasiveness with a monoclonal antibody directed against the beta-chain of the leukocyte adhesion molecule (CD18). J Immunol 150(10):4466–4477PubMed
Metadaten
Titel
Biphasic effect of a primary tumor on the growth of secondary tumor implants
verfasst von
Juan Bruzzo
Paula Chiarella
Roberto P. Meiss
Raúl A. Ruggiero
Publikationsdatum
01.10.2010
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-010-0818-7

Weitere Artikel der Ausgabe 10/2010

Journal of Cancer Research and Clinical Oncology 10/2010 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.