Elevated expression of CTRP3/cartducin contributes to promotion of osteosarcoma cell proliferation

Abstract

Abstract. CTRP3/cartducin, a novel secretory protein, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily, and plays important roles in regulating both embryonic cartilage development and postnatal longitudinal bone growth. CTRP3/cartducin is expressed in human osteosarcomas. We hypothesized that CTRP3/cartducin might have a role in osteosarcoma tumor growth and metastasis. Murine osteosarcoma cell lines, NHOS and LM8, were used as a model. RT-PCR analysis showed that the mRNA level of CTRP3/cartducin was increased in these two murine osteosarcoma cell lines compared with its level in normal murine osteoblast MC3T3-E1 cells. Western blot analysis showed that the protein level of CTRP3/cartducin was also increased in these two osteosarcoma cell lines. Stimulation of NHOS and LM8 cells by CTRP3/cartducin promoted tumor cell growth but not migration in vitro. Further, CTRP3/ cartducin stimulation led to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in these two osteosarcoma cell lines. MAPK/ERK kinase 1/2 (MEK1/2) inhibitor, U0126, blocked CTRP3/cartducin-induced cell proliferation. These results suggest that CTRP3/cartducin expression may play a role in osteosarcoma tumor growth associated with activation of the ERK1/2 signaling pathway.

New Insights Into Implications of CTRP3 in Obesity, Metabolic Dysfunction, and Cardiovascular Diseases: Potential of Therapeutic Interventions

“…CTRP3 is a new type of adipokine that can affect obesity-related cardiovascular diseases (Figure 2), which provides extensive academic research and is considered a promising therapeutic strategy. However, the following areas require further investigation: (Rosen and Spiegelman, 2006) continuous monitor of the change of CTRP3 levels in normal people, sub-clinical stage, prodromal period, clinical stage, and treatment period, and notably, excessive CTRP3 levels possibly promoting vascular calcification; (Scherer, 2006) the influences of CTRP3 on non-diabetes-related cardiomyopathy using a different method to establish study model or diabetes-related cardiomyopathy; (Akoumianakis and Antoniades, 2017) the effects of CTRP3 on pancreatic β cell, adipocyte differentiation or dedifferentiation, and muscle; (Kishore et al, 2004) the potential adverse effects: CTRP3 stimulates osteosarcoma tumor growth (Akiyama et al, 2009), and promotes the transition of prostate cells into cancer cells (Hou et al, 2015). Thus, all research results should be comprehensively evaluated before developing CTRP3 as an effective therapeutic target.…”

“…It is reported that many cell lines express CTRP3, such as mouse chondrogenic progenitor (N1511) (Maeda et al, 2006), mouse preadipocytes (3T3-L1a) (Schaffler et al, 2007;Schmid et al, 2012;Li et al, 2015), mouse osteoblast-like noncancer cell line (MC3T3-E1) (Akiyama et al, 2006), mouse osteosarcoma cell line (LM8, NOHS) (Akiyama et al, 2009), TM3 mouse Leydig cells (Otani et al, 2012), and human mesangial cells (HMCs) (Zhang et al, 2016). Even so, CTPR3 is mainly secreted by AT, and considered as an adipokine (Schaffler et al, 2003a(Schaffler et al, , 2007Wong et al, 2008).…”

“…CTRP3 has multiple effects on the metabolism (Peterson et al, 2010(Peterson et al, , 2013Zhou et al, 2014), inflammation (Weigert et al, 2005), proliferation (Yi et al, 2012), apoptosis (Song et al, 2020), vascular calcification (Zhou et al, 2014), fibrosis (Wu et al, 2015), ischemic injury , etc. (Table 1) (Akiyama et al, 2009;Kim et al, 2012;Hou et al, 2015). In this review, we summarize the role of CTRP3 in obesity, MS, T2DM, and CVD.…”

Upregulation of C1QTNF6 mediated by ncRNAs correlates with poor prognosis and immune cells infiltration of clear cell renal cell carcinoma

“…For example, C1QTNF1 not only can stimulates aldosterone production in the adrenal glands (Yamauchi et al 2001), but also inhibits collagen-induced platelet aggregation in vascular systems (Lasser et al 2006)). Activating the ERK1/2-signaling pathway, C1QTNF3 is thought to play a role in promoting osteosarcoma cell proliferation (Akiyama et al 2009).…”

Boosting hedgehog against IBD

“…Overactivation of the hedgehog pathway has been documented in many cancers, 5 including a recent report of GLI1 activation in pancreatic ductal adenocarcinoma cells. 6 Multiple companies are pursuing hedgehog antagonists, including partners Curis Inc. and Genentech Inc., which are running Phase II studies of GDC-0449 for first-line metastatic colorectal cancer, advanced basal cell carcinoma and advanced ovarian cancer.…”