Depletion of Tumor-Associated Macrophages Slows the Growth of Chemically Induced Mouse Lung Adenocarcinomas

Background. Tissue-resident macrophages can be educated to tumor-associated macrophages (TAMs) by the tumor microenvironment and many types of macrophages express erythropoietic receptor (EPOR); However, little is known about the expression of EPOR on TAMs and the identity of EPOR+ TAMs in osteosarcoma lung metastasis has thus far remained elusive. Methods. EPOR-eGFPcre mice were used to determine the expression of EPOR on lung tissue-resident macrophages. Flow cytometry, RT-PCR, and Western blot were examined to define the identity of EPOR+ TAMs in 106 osteosarcoma lung metastasis specimens. Moreover, the clinicopathologic factors and prognosis of patients with CD163+EPOR+ macrophages were compared. Results. We found that a subpopulation of mouse lung tissue-resident macrophages express EPOR and EPO enhances the proliferation of EPOR+ macrophages in mouse lung. A subpopulation of CD163+ macrophages expresses EPOR in human osteosarcoma lung metastasis specimens. CD163+EPOR+TAMs increase 2.5 times in human osteosarcoma lung metastasis tissues; CD206, CD163, and PD1, which are known to have a significant role in TAM function had high expression in CD163+EPOR+ TAMs compared with CD163+EPOR- TAMs. Furthermore, CD163+EPOR+ TAMs had higher M2 marker and cytokine expression in osteosarcoma tissues compared with para-osteosarcoma tissues. EPO enhanced the expression of M2 cytokines in primary CD163+EPOR+ TAMs. Importantly, the percentage of CD163+EPOR+ TAMs had a positive linear association with malignant phenotypes as well as poor disease-free survival and overall survival time. Conclusions. We have characterized TAMs expressing EPOR and CD163+EPOR+ macrophages as TAMs in osteosarcoma lung metastasis patients, which are highly associated with tumor aggressiveness.

Download Full-text

Detection of Retinoblastoma Gene Deletions in Spontaneous and Radiation-Induced Mouse Lung Adenocarcinomas by Polymerase Chain Reaction

Radiation Research ◽

10.2307/3578704 ◽

1994 ◽

Vol 137 (3) ◽

pp. 310 ◽

Cited By ~ 7

Author(s):

Mark E. Churchill ◽

M. Anne Gemmell ◽

Gayle E. Woloschak

Keyword(s):

Polymerase Chain Reaction ◽

Mouse Lung ◽

Retinoblastoma Gene ◽

Chain Reaction ◽

Gene Deletions ◽

Radiation Induced ◽

Polymerase Chain ◽

Lung Adenocarcinomas

Download Full-text

PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

10.2172/10149484 ◽

1994 ◽

Author(s):

M.E. Churchill ◽

M.A. Gemmell ◽

G.E. Woloschak

Keyword(s):

Pcr Detection ◽

Mouse Lung ◽

Retinoblastoma Gene ◽

Gene Deletions ◽

Radiation Induced ◽

Lung Adenocarcinomas

Download Full-text

Ultrastructural observations of lung neoplasms induced in the strain A/J mouse by benzo(a)pyrene and ethylnitrosourea

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128559 ◽

1987 ◽

Vol 45 ◽

pp. 854-855

Author(s):

W.T. Gunning ◽

G.D. Stoner ◽

P.J. Goldblatt

Keyword(s):

Histochemical Staining ◽

Clara Cell ◽

Mouse Lung ◽

Chemical Induction ◽

Cell Adenoma ◽

Alveolar Cell ◽

Chemically Induced ◽

Induced Tumors ◽

Cells Of Origin ◽

Immunocytochemical Techniques

The current literature regarding the histogenesis of mouse lung adenomas suggests two alternative cells of origin for these tumors. The Type II pneumocyte was accepted by most investigators as the cell which proliferated either spontaneously or by chemical induction, until Kauffman and co-workers reported histologic and ultrastructural features of a Clara cell adenoma, and indicated that in Swiss mice, 63% of all chemically induced tumors appeared to be Clara cell derived. Ward et al. using immunocytochemical techniques have demonstrated that all lung adenomas they tested in B6C3F1, BALB, and A strain mice appear to be of alveolar cell origin. It has also been reported that up to 70% of ethylnitrosourea induced adenomas can be characterized as Clara cell based on histochemical staining for nitroblue tetrazolium reductase.Histological investigation of lung tumors arising in Strain A/J mice from bioassays of thirteen chemicals demonstrates a variable growth pattern.

Download Full-text

MAFB is a biomarker for cancer severity, prognostic marker, and a potential target for cancer immunotherapy

10.21203/rs.3.rs-763431/v1 ◽

2021 ◽

Author(s):

Samir Omar ◽

Naohiro Kobayashi ◽

Mennatullah Siyam ◽

Manoj Yadav ◽

Yuri Inoue ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cancer Immunotherapy ◽

Prognostic Marker ◽

Mouse Tumor ◽

Tumor Associated Macrophages ◽

Potential Target ◽

Pancreatic Cancers ◽

Lung Adenocarcinomas

Abstract MAFB is a transcription factor specifically expressed in macrophages. Using in vitro and in vivo in mouse tumor models, our previous study suggested that MAFB could be a suitable marker for tumor-associated macrophages (TAMs), besides MAFB is expressed in anti-inflammatory alternatively activated M2 macrophages in vitro. TAMs play a key role in the tumor microenvironment (TME) by inducing immunosuppression, angiogenesis, tumor invasion, and metastasis. However, finding a suitable specific biomarker and target for TAMs is challenging. Here, we demonstrated that MAFB could be used as a biomarker for TAMs and consequently, for severity in various human cancers, including lung, liver, colon, and pancreatic cancers, according to the immunohistochemical analysis of the expression of MAFB, CD68, and CD204. Moreover, In a cohort of lung adenocarcinomas patients (n = 120), increased MAFB expression was related to increased tendency towards metastasis and poor overall survival rate. Further, we showed that MAFB expression was positively correlated to the expression of CD204 and CD68 in both human hepatocarcinoma and colon cancers. Our findings indicate that MAFB as a specific biomarker can be used as prognostic marker for Metastasis potential in Lung adenocarcinomas patients and also a biomarker for the severe Liver, Colon and pancreatic cancers. In addition, we showed that MAFB was expressed in Tumor associated macrophages expressing Programmed cell death protein-1 and/or Programmed cell death ligand 1 (TAM PD-1+ and TAM PD-L1+) cells in both human lung adenocarcinomas and Lewis lung carcinoma (LLC) mouse model. These findings indicate that MAFB can be a potential target for drug development against TAM PD-1+ and TAM PD-L1+ cells. In summary, transcriptional factor MAFB can be used as a specific biomarker, prognostic marker and a potential target for cancer immunotherapy against TAMs.

Download Full-text