Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292

Furugaki, Koh; Moriya, Yoichiro; Iwai, Toshiki; Yorozu, Keigo; Yanagisawa, Mieko; Kondoh, Kumiko; Fujimoto-Ohuchi, Kaori; Mori, Kazushige

doi:10.1007/s10585-011-9398-4

Cited by 43 publications

(45 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The current study showed that the expression of RANKL, not OPG, in osteoblasts was stimulated by EGF, and this might enhance osteoclast activation via the RANK/RANKL axis. This result is supported by previous study reported by Furugaki et al [33]. Using mouse osteolytic bone invasion model, they showed that the lung cancer cells induced RANKL expression of osteoblasts, and erlotinib inhibited the tumorinduced osteolytic invasion by suppressing osteoclast activation through inhibiting osteolytic factor production including RANKL.…”

Section: Discussionsupporting

confidence: 90%

Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression

Gabr

Goto

Hashimoto

et al. 2011

Clin Exp Metastasis

Self Cite

View full text Add to dashboard Cite

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show dramatic antitumor activity in a subset of patients with non-small cell lung cancer who have an active mutation in the epidermal growth factor receptor (EGFR) gene. On the other hand, some lung cancer patients with wild type EGFR also respond to EGFR-TKIs, suggesting that EGFR-TKIs have an effect on host cells as well as tumor cells. However, the effect of EGFR-TKIs on host microenvironments is largely unknown. A multiple organ metastasis model was previously established in natural killer cell-depleted severe combined immunodeficient mice using human lung cancer cells. This model was used to investigate the therapeutic efficacy of erlotinib, an EGFR-TKI, on multiple organ metastases induced by human small cell lung cancer cells (SBC-5 cells) that did not express EGFR. Although erlotinib did not have any effect on the proliferation of SBC-5 cells in vitro, it significantly suppressed bone and lung metastases in vivo, but not liver metastases. An immunohistochemical analysis revealed that, erlotinib significantly suppressed the number of osteoclasts in bone metastases, whereas no difference was seen in microvessel density. Moreover, erlotinib inhibited EGF-induced receptor activator of nuclear factor kappa-B expression in an osteoblastic cell line (MC3T3-E1 cells). These results strongly suggested that erlotinib prevented bone metastases by affecting host microenvironments irrespective of its direct effect on tumor cells.

show abstract

Section: Discussionsupporting

confidence: 90%

Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression

Gabr

Goto

Hashimoto

et al. 2011

Clin Exp Metastasis

Self Cite

View full text Add to dashboard Cite

show abstract

“…EGFR ligands stimulate osteoclast formation by inhibiting OPG expression and upregulating msRANKL 17 .…”

Section: Resultsmentioning

confidence: 99%

Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway

Taverna

Pucci

Giallombardo

et al. 2017

Sci Rep

129

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung. Its levels in plasma of NSCLC patients correlate with poor prognosis and AREG was recently found as a signaling molecule in exosomes derived from cancer cell lines. Exosomes have a key role in the cell-cell communication and they were recently indicated as important actors in metastatic niche preparation. In the present work, we hypothesize a role of AREG carried by exosomes derived from NSCLC in bone metastasis induction. We observed that NSCLC-exosomes, containing AREG, induce EGFR pathway activation in pre-osteoclasts that in turn causes an increased expression of RANKL. RANKL is able to induce the expression of proteolytic enzymes, well-known markers of osteoclastogenesis, triggering a vicious cycle in osteolytic bone metastasis.

show abstract

“…Many tumor cells with hematopoietic and epithelial origin, including colon, breast, melanoma, and non-smallcell lung cancers, were reported to directly produce IL-11 [114][115][116]. In addition, an association between an increased level of IL-11 and tumor progression was observed in different cancers, such as hepatocellular carcinoma [117], gastric carcinoma [118], pancreatic cancer [119], and renal cell carcinoma [120].…”

Section: Cancer Onset and Progressionmentioning

confidence: 99%

A panoramic review and in silico analysis of IL-11 structure and function

Negahdaripour

Nezafat

Ghasemi

2016

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292

Cited by 43 publications

References 39 publications

Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression

Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression

Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway

A panoramic review and in silico analysis of IL-11 structure and function

Contact Info

Product

Resources

About