Abstract
Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.
Highlights
Oral iron promotes intestinal tumourigenesis in animal models
This study examined for the first time in humans, two groups of anaemic patients with Colorectal cancer (CRC), randomised to oral or IV iron therapy
Despite increase in body iron following IV treatment, the effects of oral and IV iron treatments were similar in terms of iron metabolism, proliferation and apoptosis levels in tumours and paired normal tissues
Summary
Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. Intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment. Cellular absorption of dietary non-haem iron occurs in the duodenum and upper jejunum via the duodenal cytochrome b-like ferrireductase (DcytB)[4] and imported into the cell by the divalent metal transport 1 (DMT1). These cellular iron transporters are known to be present within the colonic epithelium[5] and are modified in bowel cancer[6]. Untranslated regions of messenger RNA including TfR1 and ferritin and promote the translation of TfR1 and repression of ferritin which increases the labile intracellular iron pool with decreases in iron export, utilisation and storage[14,15]
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