Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic Growth through Increased Angiogenesis

Celus, Ward; Conza, Giusy Di; Oliveira, Ana I.; Ehling, Manuel; Costa, Bruno M.; Wenes, Mathias; Mazzone, Massimiliano

doi:10.1016/j.celrep.2017.11.034

Cited by 49 publications

(42 citation statements)

References 59 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ang II receptor blockers (ARBs) are extensively used as anti-hypertensive drugs (9). Studies have reported that angiogenesis is essential for tumor progression and metastasis (10,11). Furthermore, studies have demonstrated that ARBs have the potential possibility to restrain the growth of several types of cancer cells (12,13).…”

Section: Introductionmentioning

confidence: 99%

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Expression of angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is closely associated with the occurrence and development of cancer. Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the AT2R, to mediate a series of biological effects. Telmisartan, a specific AT1R blocker, has been reported to have potential as an anticancer drug for treating renal cancer. In the present study, whether telmisartan had an effect on non-small cell lung cancer (NSCLC) cell proliferation and migration was investigated. The Cell Counting kit-8 assay revealed that telmisartan significantly inhibited the growth of the NSCLC A549 cell line in a time-and dose-dependent manner. In a transwell assay, telmisartan significantly inhibited cellular invasion and migration. Furthermore, it was determined that the expression of the anti-apoptotic protein B-cell lymphoma was decreased, and that of the pro-apoptotic proteins caspase-3 and Bcl-associated X increased in the A549 cells treated with telmisartan. Additionally, levels of phosphorylated RAC serine/threonine-protein kinase (p-AKT), p-mechanistic target of rapamycin, p70-S6 kinase and cyclin D1 was decreased in the telmisartan-treated group. Therefore, the current study reveals that telmisartan-induced NSCLC apoptosis may be regulated via the phosphoinositide 3-kinase/AKT signaling pathway, which indicates that it may be a potential novel drug for clinical NSCLC treatment. IntroductionLung cancer, the most common type of cancer, has the highest morbidity rate among all types of malignancies worldwide (1,2), accounting for 30% of all incidences of cancer-associated mortality (3). In clinical practice, the two major types of lung cancer are small cell lung cancer (SCLC) and non-SCLC (NSCLC) (4), of which NSCLC accounts for ~80% of all lung cancer cases (5). Current therapies for NSCLC include chemotherapy, radiotherapy, targeted therapy and surgery, which are used alone or in combination (6). Despite the use of these therapies, the overall 5-year survival rate of NSCLC remains low, at 15% (7). Owing to the development of drug resistance and the severe side effects experienced by patients, effective and safe novel agents are required for the treatment of NSCLC (1).Angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is a vasoconstrictor that controls cardiovascular function and renal homeostasis (8). Ang II receptor blockers (ARBs) are extensively used as anti-hypertensive drugs (9). Studies have reported that angiogenesis is essential for tumor progression and metastasis (10,11). Furthermore, studies have demonstrated that ARBs have the potential possibility to restrain the growth of several types of cancer cells (12,13). Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the Ang II type 2 receptor (AT2R), to mediate a series of biological effects (14). AT1R mediates the main functions of Ang II, including tumor growth and angiogenesis (15). Treatment with telmisartan, a spe...

show abstract

Section: Introductionmentioning

confidence: 99%

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…This was in line with a high percentage of VEGFR1 + cells found in liver metastasis patients, which correlated with worse patient outcome [100]. Conversely, a study found that calveolin-1 (Cav1) in MAMs restrains VEGF-A/VEGFR1 signaling; therefore, Cav1 depletion in MAMs promoted an increased metastatic growth and angiogenesis in lung metastatic tissue [101].…”

Section: Role Of Metastasis-associated Macrophages In Metastatic Progmentioning

confidence: 67%

Contribution of Macrophages and T Cells in Skeletal Metastasis

Mendoza-Reinoso

McCauley

Fournier

2020

Cancers

View full text Add to dashboard Cite

Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in this review as they represent a great promise for patients suffering from incurable bone metastases.

show abstract

“…Although these data should be verified in a larger case series and molecular studies, Cav-1 in the stromal component may be negatively correlated with that in BM of ADC. Recently, Cav-1 expression of fibroblast or macrophage in stromal component has been investigated in primary or secondary lung cancer [49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 enhances brain metastasis of non-small cell lung cancer, potentially in association with the epithelial-mesenchymal transition marker SNAIL

Kim

et al. 2019

Cancer Cell Int

View full text Add to dashboard Cite

Background: Caveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investigated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM). Methods: Cav-1 expression was investigated in a series of 102 BM samples and 49 paired primary NSCLC samples, as well as 162 unpaired primary NSCLC samples with (63 cases) or without (99 cases) metastasis to distant organs. Human lung cancer cell lines were used for in vitro functional analysis. Results: High Cav-1 expression in tumor cells was observed in 52% (38/73) of squamous cell carcinomas (SQCs) and 33% (45/138) of non-SQCs. In SQC, high Cav-1 expression was increased after BM in both paired and unpaired samples of lung primary tumors and BM (53% vs. 84% in paired samples, P = 0.034; 52% vs. 78% in unpaired samples, P = 0.020). Although the difference in median overall survival in patients NSCLC was not statistically significant, high Cav-1 expression in tumor cells (P = 0.005, hazard ratio 1.715, 95% confidence index 1.175-2.502) was independent prognostic factors of overall survival on multivariate Cox regression analyses, in addition to the presence of BM and non-SQC type. In vitro assays revealed that Cav-1 knockdown inhibited the invasion and migration of lung cancer cells. Genetic modulation of Cav-1 was consistently associated with SNAIL up-and down-regulation. These findings were supported by increased SNAIL and Cav-1 expression in BM samples of SQC. Conclusions: Cav-1 plays an important role in the BM of NSCLC, especially in SQC. The mechanism may be linked to SNAIL regulation.

show abstract

Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic Growth through Increased Angiogenesis

Cited by 49 publications

References 59 publications

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Contribution of Macrophages and T Cells in Skeletal Metastasis

Caveolin-1 enhances brain metastasis of non-small cell lung cancer, potentially in association with the epithelial-mesenchymal transition marker SNAIL

Contact Info

Product

Resources

About