p185neu protein is required for tumor and anchorage-independent growth, not for cell proliferation of transgenic mammary carcinoma

Nanni, Patrizia; Pupa, Serenella M.; Nicoletti, Giordano; Giovanni, Carla De; Landuzzi, Lorena; Rossi, Ilaria; Astolfi, Annalisa; Ricci, Cinzia; Vecchi, R.; Invernizzi, Anna M.; Carlo, Emma Di; Musiani, Piero; Forni, Guido; Ménard, Sylvie; Lollini, Pier Luigi

doi:10.1002/1097-0215(20000715)87:2<186::aid-ijc5>3.0.co;2-1

Cited by 75 publications

(42 citation statements)

References 27 publications

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“…TS/A and TUBO mouse mammary carcinoma cell lines were derived from a BALB/c background and were gifts from Dr. Patrizia Nanni (University of Bologna, Bologna, Italy) 34,35 and were grown in Dulbecco’s modified Eagle medium (DMEM, BioSource, Inc., Gaithersburg, MD) with 10% fetal bovine serum (FBS; Gemini, Calabassas, CA) and 10 μg/mL gentamicin sulfate (BioSource). Human embryonic kidney (HEK-293) cells and murine TRAMP-C2 prostate cancer cells were purchased from the American Type Culture Collection (ATCC, Manassas, VA) and were grown in DMEM with 10% FBS and 10 μg/mL gentamicin sulfate (BioSource).…”

Section: Methodsmentioning

confidence: 99%

Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer

et al. 2014

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A number of antitumor vaccines have shown recent promise up-regulating immune responses against tumor antigens and improving patient survival. In this study we examine the effectiveness of vaccination using IL-15 expressing tumor cells and examined their ability to up-regulate immune responses to tumor antigens. We demonstrated that the co-expression of IL-15 with its receptor, IL-15Rα, increased the cell-surface expression and secretion of IL-15. We show that a gene transfer approach using recombinant adenovirus to express IL-15 and IL-15Rα in murine TRAMP-C2 prostate or TS/A breast tumors induced antitumor immune responses. From this we developed a vaccine platform, consisting of TRAMP-C2 prostate cancer cells or TS/A breast cancer cells co-expressing IL-15 and IL-15Rα that inhibited tumor formation when mice were challenged with tumor. Inhibition of tumor growth led to improved survival when compared to animals receiving cells expressing IL-15 alone or unmodified tumor cells. Animals vaccinated with tumor cells co-expressing IL-15 and IL-15Rα showed greater tumor infiltration with CD8+ T and NK cells, as well as increased antitumor CD8+ T-cell responses. Vaccination with IL-15/IL-15Rα-modified TS/A breast cancer cells provided a survival advantage to mice challenged with unrelated murine TUBO breast cancer cells indicating the potential for allogeneic IL-15/IL-15Rα expressing vaccines.

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Section: Methodsmentioning

confidence: 99%

Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer

et al. 2014

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“…N202.1A mammary cancer cells, derived from a Tg-neu tumor [51], were provided by Dr Vincenzo Bronte (Verona University, Italy) and cultured as described [29]. …”

Section: Methodsmentioning

confidence: 99%

A lovastatin-elicited genetic program inhibits M2 macrophage polarization and enhances T cell infiltration into spontaneous mouse mammary tumors

et al. 2013

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Beyond their ability to inhibit cholesterol biosynthesis, the statins have pleiotropic effects that include anti-inflammatory and immunomodulatory activities. Statins could have clinical utility, alone or in combination with other chemotherapeutics, in the treatment of cancer. The mechanisms that underlie the anti-tumor activity of the statins are nonetheless poorly defined. No studies have analyzed how they alter the tumor-associated leukocyte infiltrate, a central factor that influences tumor stroma and cancer evolution. Here we used HER2/neu transgenic (Tg-neu) mice to analyze the effect of lovastatin (Lov) on the inflammatory reaction of spontaneous mammary tumors. Lov treatment of tumor-bearing Tg-neu mice did not alter growth of established tumors, but significantly reduced the number of new oncogenic lesions in these mice. Moreover, Lov inhibited the growth of newly implanted Tg-neu tumors in immunocompetent but not in immunodeficient mice. We found that Lov enhanced tumor infiltration by effector T cells, and reduced the number of immunosuppressive and pro-angiogenic M2-like tumor-associated macrophages (TAM). Concomitantly, the drug improved the structure and function of the tumor vasculature, measured as enhanced tumor oxygenation and penetration of cytotoxic drugs. Microarray analysis identified a Lov-elicited genetic program in Tg-neu tumors that might explain these effects; we observed Lov-induced downregulation of placental growth factor, which triggers aberrant angiogenesis and M2-like TAM polarization. Our results identify a role for lovastatin in the shaping and re-education of the inflammatory infiltrate in tumors, with functional consequences in angiogenesis and antitumor immunity.

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“…The parental murine breast cancer cell line, N202.1A 48 was stably transfected to express GFP under histone H2B promoter 49 . The two cell lines, N202.1A parental and N202.1A+H2B-GFP (obtained from Drs.…”

Section: Methodsmentioning

confidence: 99%

I. Embryonal vasculature formation recapitulated in transgenic mammary tumor spheroids implanted pseudo-orthotopicly into mouse dorsal skin fold: the organoblasts concept

Witkiewicz

Schnitzer

2013

F1000Res

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Inadequate understanding of cancer biology is a problem. This work focused on cellular mechanisms of tumor vascularization. According to earlier studies, the tumor vasculature derives from host endothelial cells (angiogenesis) or their precursors of bone marrow origin circulating in the blood (neo-vasculogenesis) unlike in embryos. In this study, we observed the neo-vasculature form in multiple ways from local precursor cells. Recapitulation of primitive as well as advanced embryonal stages of vasculature formation followed co-implantation of avascular ( in vitro cultured) N202 breast tumor spheroids and homologous tissue grafts into mouse dorsal skin chambers. Ultrastructural and immunocytochemical analysis of tissue sections exposed the interactions between the tumor and the graft tissue stem cells. It revealed details of vasculature morphogenesis not seen before in either tumors or embryos. A gradual increase in complexity of the vascular morphogenesis at the tumor site reflected a range of steps in ontogenic evolution of the differentiating cells. Malignant- and surgical injury repair-related tissue growth prompted local cells to initiate extramedullar erythropoiesis and vascular patterning. The new findings included: interdependence between the extramedullar hematopoiesis and assembly of new vessels (both from the locally differentiating precursors); nucleo-cytoplasmic conversion (karyolysis) as the mechanism of erythroblast enucleation; the role of megakaryocytes and platelets in vascular pattern formation before emergence of endothelial cells; lineage relationships between hematopoietic and endothelial cells; the role of extracellular calmyrin in tissue morphogenesis; and calmyrite, a new ultrastructural entity associated with anaerobic energy metabolism. The central role of the extramedullar erythropoiesis in the formation of new vasculature (blood and vessels) emerged here as part of the tissue building process including the lymphatic system and nerves, and suggests a cellular mechanism for instigating variable properties of endothelial surfaces in different organs. Those findings are consistent with the organoblasts concept, previously discussed in a study on childhood tumors, and have implications for tissue definition.

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p185neu protein is required for tumor and anchorage-independent growth, not for cell proliferation of transgenic mammary carcinoma

Cited by 75 publications

References 27 publications

Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer

Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer

A lovastatin-elicited genetic program inhibits M2 macrophage polarization and enhances T cell infiltration into spontaneous mouse mammary tumors

I. Embryonal vasculature formation recapitulated in transgenic mammary tumor spheroids implanted pseudo-orthotopicly into mouse dorsal skin fold: the organoblasts concept

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