BMP6 and BMP4 expression in patients with cancer-related anemia and its relationship with hepcidin and s-HJV

Abstract

ABSTRACT. In the present study, we investigated BMP6 and BMP4 expression in patients with cancer-related anemia (CRA) as well as its relationship with hepcidin and s-HJV. The avidin-biotin system enzymelinked immunosorbent assay was used to test serum levels of BMP6, BMP4, s-HJV, and hepcidin in 53 cancer patients with anemia and 52 control cancer patients without anemia. Serum levels of BMP6 and hepcidin in the anemia group were 434.53 ± 212.11 ng/mL and 5.68 ± 3.89 µg/L, respectively. In the non-anemia cancer group, serum BMP6 and hepcidin levels were 334.37 ± 171.32 ng/mL and 4.60 ± 2.28 µg/L, which were significantly lower than the levels for the CRA group (P < 0.05). In addition, the serum level of s-HJV was 0.69 ± 0.28 ng/mL in the CRA group, which was significantly lower compared to that for the nonanemia group (1.07 ± 1.00 ng/mL, P < 0.01). There were no significant differences in BMP4 expression between the two groups. BMP6 was negatively correlated with s-HJV and Hb (r = -0.2536 and -0.2949, P < 0.01), but was not correlated with hepcidin. Similarly, BMP4 expression was not correlated with Hb, s-HJV, or hepcidin. Our study shows that patients with CRA had high expression of BMP6 and hepcidin and low expression of s-HJV. BMP6 was found to be negatively correlated with s-HJV; both regulate hepcidin expression and play important roles in the development of anemia.

Expression of Hepcidin and Neogenin in colorectal cancer

“…Elevated expression of Hepcidin can inhibit the intestinal iron absorption and inhibit the release of iron from the mononuclear macrophage system, which makes the iron storage in the cells, iron reduction in bone marrow, and ultimately lead to iron loss and anemia [18,20-22]. Our previous studies [19] also showed that Hepcidin plays an important role in the treatment of postoperative radiotherapy and chemotherapy in patients with advanced tumor anemia, the expression of hepcidin in patients with anemia was significantly higher compared with that of patients without anemia (P<0.05), which was negatively correlated with Hb (r =-0.2597,P<0.01).…”

“…Anemia is one of the common symptoms in patients with intestinal tumor. It is generally considered that the anemia is a chronic disease in chronic inflammation and malignant tumors (ACD), Current research [ 17 - 19 ] has confirmed that Hepcidin plays a key role in the occurrence and development of ACD [ 17 ]. Elevated expression of Hepcidin can inhibit the intestinal iron absorption and inhibit the release of iron from the mononuclear macrophage system, which makes the iron storage in the cells, iron reduction in bone marrow, and ultimately lead to iron loss and anemia [ 18 , 20 - 22 ].…”

The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function

“…Both BMP9 and BMP10 have relatively high circulating levels in blood (~ 0.5-15 ng/mL) in both humans and mice [24,28,[41][42][43][44][45], indicating that they are delivered to endothelial cells via the bloodstream. BMP2, BMP4, and BMP6 serum levels are much lower (pg/ mL-low ng/mL range) [43,46,47] and are expressed in a temporally and spatially regulated manner developmentally [32,48], indicating paracrine interactions that affect endothelial cell behaviors. Interestingly, BMP2 and BMP4 mRNA and protein are also expressed in endothelial cells, suggesting autocrine or paracrine vascular effects that have not been well-explored [49][50][51][52][53][54][55].…”

TAM-ing the CIA—Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia

“…BMP-6 is secreted by endothelial cells in the liver to inform adjacent hepatocytes about elevated serum iron levels and replenished iron stores (110). Accordingly, BMP-6 is a major inducer of HAMP transcription and a potential mediator of CIA (111)(112)(113). Given the key role of BMP-6 for the induction of hepcidin, it is not surprising that neutralizing antibodies have been used to block hepcidin induction in preclinical and clinical models of ACD (114)(115)(116).…”

“…BMP-6 and hepcidin levels are elevated in CIA which may aid in the diagnosis ( 112 , 113 ). Yet it remains unclear whether serum concentrations of these mediators predict the response to currently available treatments such as ESA and to therapies specifically targeting them ( 172 ).…”