Expression of lactoferrin in human stomach (original) (raw)
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In Vitro, 1984
Lactoferrin was examined for its effect on the growth of a human colon adenocarcinoma cell line {HT 29) in culture and its action was compared to that produced by transferrin and two different iron solutions iferrous sulfate and ferric chloridej. When transferrin was replaced by either iron solutions the cell grew in proportion to the quantity added and the maximal effect obtained was identical to that produced by transferrin alone. When transferrin was replaced by lactoferrin the cells were unable to proliferate for a long time. However, in the presence of low-concentration iron solutions, lactoferrin stimulated the cell growth, and the effect was more pronounced with the ferric chloride solution.
Lactoferrin and Cancer Disease Prevention
Critical Reviews in Food Science and Nutrition, 2008
Lactoferrin (LF) is an iron-binding glycoprotein that composes the transferrin family and is predominantly found in the products of the exocrine glands located in the gateways of the digestive, respiratory and reproductive systems, suggesting a role in the non-specific defence against invading pathogens. Additionally, several physiological roles have been attributed to LF, namely regulation of iron homeostasis, host defence against infection and inflammation, regulation of cellular growth and differentiation and protection against cancer development and metastasis. These findings have suggested LF's great potential therapeutic use in cancer disease prevention and/or treatment, namely as a chemopreventive agent. This review looks at the recent advances in understanding the mechanisms underlying the multifunctional roles of LF and future perspectives on its potential therapeutic applications.
Pediatric Research, 2007
Human milk stimulates intestinal development through the effects of various moieties. Lactoferrin (LF) is a glycoprotein of human milk whose concentration is highest in colostrum decreasing in mature milk. LF promotes enterocyte growth in intestinal cell lines. We tested the hypothesis that LF induces a distinct effect on enterocyte proliferation and differentiation, depending on its concentration. We examined the dose-related effects by humannative LF (N-LF) in Caco-2 (human colon adenocarcinoma) cells. At high concentrations, N-LF stimulated cell proliferation in immature Caco-2 cells, as judged by 3 H-thymidine incorporation. In contrast, sucrase and lactase activities were increased at low but not high LF concentrations and their mRNA were also increased, indicating a transcriptional effect. Because iron binds specific LF sites, we compared the potency of N-LF and iron-saturated LF (I-LF) and found the native form more potent. Finally, we tested the effects by bovine LF (bLF) in the same system and found the latter more potent than the human isoform in inducing cell growth and lactase expression. These results suggest that LF directly induces enterocyte growth and proliferation, depending on its concentration, thereby regulating the earlyx postnatal intestinal development. bLF could be added to infant formula as a growth factor in selected intestinal diseases.
Cancers
The connection between inflammation and cancer is well-established and supported by genetic, pharmacological and epidemiological data. The inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, have been described as important promoters for colorectal cancer development. Risk factors include environmental and food-borne mutagens, dysbalance of intestinal microbiome composition and chronic intestinal inflammation, with loss of intestinal epithelial barrier and enhanced cell proliferation rate. Therapies aimed at shutting down mucosal inflammatory response represent the foundation for IBDs treatment. However, when applied for long periods, they can alter the immune system and promote microbiome dysbiosis and carcinogenesis. Therefore, it is imperative to find new safe substances acting as both potent anti-inflammatory and anti-pathogen agents. Lactoferrin (Lf), an iron-binding glycoprotein essential in innate immunity, is generally recognized as safe and...
Immunohistochemical Investigation of Lactoferrin in Human Bone Primary and Metastatic Tumours
International Journal of Laboratory Medicine & Research, 2015
Background: Lactoferrin (LF), an iron-binding glycoprotein, has a multifunctional role in humans, specifically in the regulation of iron homeostasis, host defense against infections and inflammations, even if some experimental studies attributed others activities to LF, such as cellular differentiation, regulation growth, protection against cancer development and metastases. Methods: We performed herein an immunohistochemical analysis of LF in a cohort of primary and metastatic neoplasms occurred in the bone by using a monoclonal specific antibody. LF reactivity was quantified using an intensity-distribution (ID) score. Results: In primary bone tumours, LF immunostaining as whole was evident in 21/82 cases (25.60%), either benign or malignant. About bone metastatic lesions, LF immunopositivity was encountered in 14/30 cases (46.6%), mainly due to prostatic, renal, uterine and colonic carcinomas, while the positivity was reduced in metastases from breast carcinomas and it was completely absent in lung cancer. Conclusion: On the light of these results, we suggest that neoplastic elements might produce LF in order to make a greater amount of iron available for their turnover. Additional analyses are needed concerning new applications of LF in clinical oncology either for its nutraceutical function either for its capability to potentiate chemotherapy.
The Biological Properties of Lactoferrin
Central European Journal of Sport Sciences and Medicine, 2016
Lactoferrin (LF) is an iron-binding glycoprotein from the transferrin family, which has been identified in most biological fluids as secretions from exocrine glands and the content of specific granules of neutrophils. It has been reported to have numerous functions. Due to antimicrobial and anti-inflammatory activity, the lactoferrin plays significant role in host defense against infection and extreme inflammation. Recent studies have also demonstrated that LF can protect against cancer in experimental animals and has anticarcinogenic activity in many human tumors. At the cellular level, LF modulates the proliferation, differentiation, maturation, activation, migration and function of immune cells. This review presents the multifunctional roles and specific beneficial properties of lactoferrin.
Isolation of a lactoferrin cDNA clone and its expression in human breast cancer
British journal of cancer, 1992
A cDNA library constructed from mRNA from a human breast carcinoma metastasis was screened with a polyclonal antibody to deglycosylated human milk fat globule membrane, resulting in the isolation of eight clones from a total of 10(5) plaques. One of these (J16) was identified as lactoferrin. It was highly expressed (as a 2.5 Kb mRNA) in lactating breast and in both normal resting tissue taken from adjacent to carcinoma or from reduction mammoplasties. Immunoreactive lactoferrin was localised to ductal cells and their secretions in both normal and mildly hyperplastic ducts. In a normal tissue screen J16 was highly expressed in stomach, poorly in skin and lymphocytes and absent from other organs examined. It was variably expressed in 33/59 invasive primary breast tumours; lactoferrin protein in these was heterogeneously distributed in epithelial tumour foci. Presence of J16 was inversely related to expression of oestrogen receptor protein (P = 0.0001). There was no significant relatio...
Lactoferrin, an Iron-Binbing Protein Ni Neutrophilic Leukocytes
Journal of Experimental Medicine, 1969
In 1939 a red protein was discovered in bovine milk by S¢rensen and SCrensen (1). It has recently been isolated and its physicochemical features were described by several workers who investigated the bovine component (2, 3), as well as its human homologue (4-8). This protein has been given various names, such as lactoferrin (9), lactotransferrin (10), lactosiderophilin (10), or ekkrinosiderophilin (11). It shares with serum transferrin the property of reversibly binding two atoms of iron. However, the two proteins differ greatly in their antigenic properties (6, 7) and chemical composition (12-16). On account of its absence in serum, lactoferrin has been regarded as a specific milk protein until 1963 when Biserte et al. (17) reported its occurrence in the sputum of bronchitis patients. Using immunological methods, it has also been possible to demonstrate the presence of lactoferrin in various other biological fluids, as tears, saliva, nasal and bronchial secretions, gastrointestinal fluid, hepatic bile, urine, seminal fluid, and cervical mucus (18). Taken together, these findings have created the impression that lactoferrin is chiefly an epithelial secretion product. Recent investigations on guinea pig tissues have however shown that the spleen and bone marrow are rich sources of lactoferrin (unpublished). Furthermore, immunohistochemical observations on certain human tissues, the uterine cervix for example, suggest that glandular epithelia are not the only sites of origin for lactoferrin in external secretions and that certain blood cells may also be implicated in the production of this protein (19).
Anticancer effects of lactoferrin: underlying mechanisms and future trends in cancer therapy
Lactoferrin has been widely studied over the last 70 years, and its role in diverse biological functions is now well known and generally accepted by the scientific community. Usually, alterations of the lactoferrin gene in cells are associated with an increased incidence of cancer. Several studies suggest that exogenous treatment with lactoferrin and its derivatives can efficiently inhibit the growth of tumors and reduce susceptibility to cancer. None of these studies, however, reported a consistent outcome with regard to the mechanisms underlying the anticancer effects of lactoferrin. In this review, the association of lactoferrin with cancer is thoroughly discussed, from lactoferrin gene expression to the potential use of lactoferrin in cancer therapy. Lactoferrin cytotoxicity against several cancers is reported to occur in distinct ways under different conditions, namely by cell membrane disruption, apoptosis induction, cell cycle arrest, and cell immunoreaction. Based on these mechanisms, new strategies to improve the anticancer effects of the lactoferrin protein and/or its derivatives are proposed. The potential for lactoferrin in the field of cancer research (including as a chemotherapeutic agent in cancer therapy) is also discussed.
The binding of human lactoferrin to mouse peritoneal cells
Journal of Experimental Medicine, 1976
Human iron-saturated Lf (FeLf), which was labeled with 125I or 50Fe, was found to combine with the membrane of mouse peritoneal cells (MPC) which consisted of 70% macrophages. The following experimental data suggested the involvement of a specific receptor. (a) The binding of FeLf to MPC reached a saturation point. (b) The binding of radioactive FeLf was inhibited by preincubating the cells with cold FeLf but not with human Tf, human aggregated and nonaggregated IgG, or beef heart cytochrome c (c) Succinylation and carbamylation of FeLf resulted in a loss of its inhibiting activity on the binding of radioactive FeLf. Removal of neuraminic acid from FeLf increased its inhibitory activity. (d) The ability of apoLf to inhibit the binding of FeLf to MPC was significantly lower than that of FeLf. The existence of a Lf receptor capable of concentrating Lf released from neutrophils on the membrane of macrophages could explain the apparent blockade of the release of iron from the reticuloen...