Spontaneous murine lung adenocarcinoma (P07): A new experimental model to study paraneoplastic syndromes of lung cancer.

Diament, Miriam J.; García, C. Blanco; Stillitani, Isabel; Saavedra, Victoria; Manzur, T; Vauthay, Liliana; Klein, Slobodanka

doi:10.3892/ijmm.2.1.45

Cited by 16 publications

(27 citation statements)

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“…This cell line was obtained in vitro, after different passages of a P07 primary culture in previous studies [20][21][22]. LP07 cell line shares identical characteristics with the P07 tumor regarding both lung tumor incidence and histology [20][21][22]. Moreover, one month after tumor transplantation, all animals developed lung metastasis and spleen enlargement without affecting other organs [20][21][22][23]25].…”

Section: Animal Experimentsmentioning

confidence: 99%

Section: Animal Experimentsmentioning

confidence: 99%

“…The LP07 cell line derives from the P07 lung tumor, which spontaneously arose in the lungs of BALB/c mice [20]. This cell line was obtained in vitro, after different passages of a P07 primary culture in previous studies [20][21][22]. LP07 cell line shares identical characteristics with the P07 tumor regarding both lung tumor incidence and histology [20][21][22].…”

Section: Animal Experimentsmentioning

confidence: 99%

“…Thus, key biological events such as cell proliferation, redox balance, inflammation, apoptosis, and autophagy were analyzed in the subcutaneous tumors of lung adenocarcinoma cells in BALB/c mice in response to several pharmacological agents that directly influence tumor growth and survival, namely the antioxidant N-acetyl cysteine (NAC), and the inhibitors of MAPK (MEK), NF-κB, and proteasome pathways: U0126, sulfasalazine, and bortezomib, respectively. The current model has been previously validated [20][21][22][23][24], and is the only approach to obtain sufficient material to warrant the reliability of the biological determinations in the tumors, since they would have not been possibly analyzed in the lung micrometastasis of the experimental mice.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology

Mateu-Jiménez¹,

Fermoselle²,

Rojo³

et al. 2016

CPD

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Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF-κB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-κB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07 adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-κB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutanous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67).Inflammation and NF-κB p65 expression were attenuated by NF-κB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-κB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.Word count: 250

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Section: Animal Experimentsmentioning

confidence: 99%

Section: Animal Experimentsmentioning

confidence: 99%

Section: Animal Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology

Mateu-Jiménez¹,

Fermoselle²,

Rojo³

et al. 2016

CPD

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“…19,20 We have been studying a murine lung adenocarcinoma, P07, that induces in the host leukocytosis, cachexia and hypercalcemia. 21 We detected GM-CSF and IL-6 in tumor conditioned media and PTHrP in plasma samples of tumor-bearing mice. 22 These factors might partly account for the above-mentioned syndromes.…”

mentioning

confidence: 81%

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

Peluffo

Stillitani

Rodríguez

et al. 2004

Intl Journal of Cancer

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Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1␤ and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies.

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Pharmacological Strategies in Lung Cancer-Induced Cachexia: Effects on Muscle Proteolysis, Autophagy, Structure, and Weakness

et al. 2014

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Cachexia is a relevant comorbid condition of chronic diseases including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-κB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-κB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-κB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-κB and MAPK, but not the proteasome system, induced in cancer cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. Attenuation of MAPK and NF-κB signaling pathway effects on muscles is beneficial in cancer-induced cachexia.

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Spontaneous murine lung adenocarcinoma (P07): A new experimental model to study paraneoplastic syndromes of lung cancer.

Cited by 16 publications

References 0 publications

Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology

Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

Pharmacological Strategies in Lung Cancer-Induced Cachexia: Effects on Muscle Proteolysis, Autophagy, Structure, and Weakness

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