Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficientop/op mouse: Evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma

Nowicki, Andrzej; Szenajch, Jolanta; Ostrowska, Grazyna; Wójtowicz, Andrzej; Wójtowicz, Katarzyna; Kruszewski, Adam A.; Maruszyński, Marek; Aukerman, Sharon L.; Wiktor-Jedrzejczak, W

doi:10.1002/(sici)1097-0215(19960103)65:1<112::aid-ijc19>3.0.co;2-i

Cited by 114 publications

(71 citation statements)

References 14 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TIM and TAM have been reported to produce a variety of cytokines in vivo which support tumor growth, including TGF␤ and MIF (8,14). In the current study, this was extended to demonstrate that treatment of TAM with IL-12 in vitro or in vivo up-regulated IL-15 and IL-18 gene expression and down-regulated TGF␤ and MIF gene expression.…”

Section: Discussionsupporting

confidence: 55%

“…Both tumor-infiltrating macrophages (TIM) 3 and tumor-associated macrophages (TAM) have been described as suppressor macrophages that display antiinflammatory and immunosuppressive activities (9,(11)(12)(13). TIM and TAM also display activities, which appear to be required for tumor growth and metastasis, including production of MCP-1, migration inhibitory factor (MIF), and TGF␤ (8,14). Thus, if TIM and TAM retained functional plasticity, they would potentially be useful targets for tumor therapy regimens because redirecting their functional activities could reduce support for tumor metastasis and reduce suppressive influence of the tumor and TAM on the adaptive immune system.…”

Section: Il-12 Rapidly Alters the Functional Profile Of Tumor-associamentioning

confidence: 99%

See 1 more Smart Citation

IL-12 Rapidly Alters the Functional Profile of Tumor-Associated and Tumor-Infiltrating Macrophages In Vitro and In Vivo

Watkins

Egilmez

Suttles

et al. 2007

The Journal of Immunology

231

190

View full text Add to dashboard Cite

Tumor-associated macrophages (TAMs) play a major role in promoting tumor growth and metastasis and in suppressing the antitumor immune response. Despite the immunosuppressive environment created by the tumor and enforced by tumor-associated macrophages, treatment of tumor-bearing mice with IL-12 induces tumor regression associated with appearance of activated NK cells and activated tumor-specific CTLs. We therefore tested the hypothesis that IL-12 treatment could alter the function of these tumor-associated suppressor macrophages. Analysis of tumor-infiltrating macrophages and distal TAMs revealed that IL-12, both in vivo and in vitro, induced a rapid (<90 min) reduction of tumor supportive macrophage activities (IL-10, MCP-1, migration inhibitory factor, and TGFβ production) and a concomitant increase in proinflammatory and proimmunogenic activities (TNF-α, IL-15, and IL-18 production). Similar shifts in functional phenotype were induced by IL-12 in tumor-infiltrating macrophages isolated from the primary tumor mass and in TAMs isolated from lung containing metastases, spleen, and peritoneal cavity. Therefore, although TAMs display a strongly polarized immunosuppressive functional profile, they retain the ability to change their functional profile to proinflammatory activities given the appropriate stimulus. The ability of IL-12 to initiate this functional conversion may contribute to early amplification of the subsequent destructive antitumor immune response.

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Il-12 Rapidly Alters the Functional Profile Of Tumor-associamentioning

confidence: 99%

IL-12 Rapidly Alters the Functional Profile of Tumor-Associated and Tumor-Infiltrating Macrophages In Vitro and In Vivo

Watkins

Egilmez

Suttles

et al. 2007

The Journal of Immunology

231

190

View full text Add to dashboard Cite

show abstract

“…In contrast, overexpression of CSF-1 in the tumour dramatically increased the macrophage density in the primary tumour and this was correlated with an accelerated malignant switch (Lin et al, 2001). Similarly, removal of CSF-1 from transplanted tumours also resulted in an impairment of growth with extensive necrosis and poor vascularisation, phenotypes that could be reversed by treatment of the mice with CSF-1 (Nowicki et al, 1996). These studies have provided strong evidence that TAMs promote the tumour progression to malignancy.…”

Section: Macrophagesmentioning

confidence: 89%

Role of infiltrated leucocytes in tumour growth and spread

2004

View full text Add to dashboard Cite

Leucocytes are a major component of the tumour microenvironment. Recent studies have indicated that the infiltration and activity of these host cells are regulated by the tumour to promote its survival and progression. Through the production of an array of growth factors, proteases and angiogenic mediators, leucocytes in the tumour microenvironment promote tumour growth, angiogenesis and metastasis.

show abstract

“…2). In response to tumor microenvironments, macrophages elaborate growth factors, and immune suppressive cytokines (3,4), and a growing body of evidence suggests macrophages promote tumor angiogenesis and progression (5)(6)(7)(8)(9)(10)(11)(12). Several preclinical studies have shown tumor growth suppression by chemical or genetic depletion of TAMs (8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Of particular relevance, TAM numbers were greatly reduced in developing mammary carcinomas in CSF-1-deficient mice compared with carcinomas in mice with normal CSF-1 expression (6). A role for CSF-1-dependent TAMs in tumor growth was first inferred by the poor growth of Lewis lung carcinomas in CSF-1-deficient mice (7), whereas parenteral administration of recombinant CSF-1 accelerated tumor growth in wild-type mice (16). CSF-1 antisense oligonucleotides or neutralizing antibody have reduced the growth rates of colon, germline, and mammary carcinoma xenografts (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia

Manthey

Johnson

Illig

et al. 2009

Molecular Cancer Therapeutics

103

View full text Add to dashboard Cite

There is increasing evidence that tumor-associated macrophages promote the malignancy of some cancers. Colonystimulating factor-1 (CSF-1) is expressed by many tumors and is a growth factor for macrophages and mediates osteoclast differentiation. Herein, we report the efficacy of a novel orally active CSF-1 receptor (CSF-1R) kinase inhibitor, JNJ-28312141, in proof of concept studies of solid tumor growth and tumor-induced bone erosion. H460 lung adenocarcinoma cells did not express CSF-1R and were not growth inhibited by JNJ-28312141 in vitro. Nevertheless, daily p.o. administration of JNJ-28312141 caused dose-dependent suppression of H460 tumor growth in nude mice that correlated with marked reductions in F4/ 80 + tumor-associated macrophages and with increased plasma CSF-1, a possible biomarker of CSF-1R inhibition. Furthermore, the tumor microvasculature was reduced in JNJ-28312141-treated mice, consistent with a role for macrophages in tumor angiogenesis. In separate studies, JNJ-28312141 was compared with zoledronate in a model in which MRMT-1 mammary carcinoma cells inoculated into the tibias of rats led to severe cortical and trabecular bone lesions. Both agents reduced tumor growth and preserved bone. However, JNJ-28312141 reduced the number of tumor-associated osteoclasts superior to zoledronate. JNJ-28312141 exhibited additional activity against FMS-related receptor tyrosine kinase-3 (FLT3). To more fully define the therapeutic potential of this new agent, JNJ-28312141 was evaluated in a FLT3-dependent acute myeloid leukemia tumor xenograft model and caused tumor regression. In summary, this novel CSF-1R/FLT3 inhibitor represents a new agent with potential therapeutic activity in acute myeloid leukemia and in settings where CSF-1-dependent macrophages and osteoclasts contribute to tumor growth and skeletal events.

show abstract

Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficientop/op mouse: Evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma

Abstract: o 1996 Wiley-Liss, Inc.

Cited by 114 publications

References 14 publications

IL-12 Rapidly Alters the Functional Profile of Tumor-Associated and Tumor-Infiltrating Macrophages In Vitro and In Vivo

IL-12 Rapidly Alters the Functional Profile of Tumor-Associated and Tumor-Infiltrating Macrophages In Vitro and In Vivo

Role of infiltrated leucocytes in tumour growth and spread

JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia

Contact Info

Product

Resources

About