Cancer patients who frequently eat peanuts may be at increased risk of their cancer spreading


A study by University of Liverpool researchers has identified new factors accompanying previous findings that frequent consumption of peanuts by cancer patients could increase risk of cancer spread.

The study, published in Carcinogenesis, shows that Peanut agglutinin (PNA) — a carbohydrate-binding protein that rapidly enters into the blood circulation after peanuts are eaten — interacts with blood vascular wall (endothelial) cells to produce molecules called cytokines.

The cytokines in question, IL-6 and MCP-1 are well-known promoters of cancer metastasis. The increased cytokine production causes other endothelial cells to express more cell surface adhesion molecules, making them more attractive to the circulating tumour cells and thus potentially promoting metastasis.

In an earlier study, Corresponding Author Professor Lu-Gang Yu and colleagues reported that circulating PNA binds to a special sugar chain, which occurs mainly on pre-cancerous and cancer cells, and interacts with a larger protein expressed on the surface of tumour cells in the bloodstream.

This interaction triggers changes in the larger protein, resulting in underlying adhesion molecules on the surface of the cancer cell to become exposed, making the cancer cells stickier and easier to attach themselves to the blood vessels. It also allows the cancer cells to form small clumps that prolong the survival of cancer cells in the body’s circulation.

Many epithelial cancers spread to the other organs through traveling through the bloodstream.

Professor Lugang Yu said: “Although further research and investigation are still needed, these studies suggest that very frequent consumption of peanuts by cancer patients might increase the risk of metastatic spread.

“Reassuringly though, a large US study reported no significant impact of peanut consumption on cancer mortality. In another study, peanut consumption was reported to have no significant effect on prognosis in men with established prostate cancer.

In our previous healthy volunteer study, substantial blood concentrations of PNA were only seen transiently one hour or so after consumption of a large dose (250g) of peanuts, so it may be that ‘normal’ peanut consumption yielding lower PNA concentrations is harmless.

“Nevertheless, the possibility remains that circulating PNA, at least at the relatively high levels found shortly after a large “dose” of peanuts, could have a significant biological effect on tumour cells circulating at that time, with a potential for increased risk of metastasis. Heavy or very frequent peanut consumption therefore might be better avoided by cancer patients.”

The possible impact of heavy peanut consumption by cancer patients on survival will need to be investigated in further population-based epidemiological studies.

Funding: This study was supported by the American Institute for Cancer Research.

Peanut Agglutinin

General and structure

Peanut agglutinin (PNA) is a common dietary lectin and is derived from the peanut, Arachis hypogea. The molecular weight of PNA is about 110 kDa and it is a homo-tetrameric protein with four parallel chains each of 27 kDa. [154] PNA accounts for 0.15% of the total peanut weight and is highly resistant to degradation during cooking or digestion by gastric acid and enzymes in the small intestine. [155] Consequently it can be recovered in active form from faeces. Moreover, and remarkably, PNA rapidly enters the blood circulation in intact form after peanut ingestion.

After ingestion of peanuts, intact PNA can be detected at 5µg/ml in the systemic circulation at 1-hour time point. [156] It presumably gains entry by binding to epithelial surface ligands followed by internalisation but the exact site and mechanism are unknown. The overall effect of the uptake of intact dietary lectins into the circulation might lead to important interactions with circulation and cellular glycoproteins and, therefore, affect cell-to-cell adhesion and proliferation. [157-159]

Previous studies have provided considerable epidemiological evidence for the role of diet in colorectal cancer causation. Patients who consumed 100g peanuts per day for five days were found on rectal biopsy to show considerable increase in epithelial proliferation. PNA remains active in roasted peanuts.[160]
Moreover there is increased expression of TF antigen in hyperplastic and neoplastic colonic epithelial cells in vitro and in vivo. [161]

PNA is shown to bind to many abnormal glycosylation sites on the tumour cell surface leading to homotypic and heterotypic cell adhesion that could potentially promote cancer metastasis. [162] In colon cancer, alterations in epithelial cell surface carbohydrate expression are common and are significant examples of abnormal neo-expression of oncofetal antigens. [163]

These changes also happen in hyperplasia and malignancy. [161, 164] All these variations can be detected by different specific patterns of lectin-ligand binding. Previous study by our group has shown that PNA has mitogenic effects on normal colorectal epithelium, if low level TF expression is present, and on HT29 colorectal cancer cells.

In addition, PNA has also been studied in lymphoid and some vascular muscle cells showing mitogenic effects. [165] PNA binding to endothelial cells is increased in colonic cancer and adenomas, whereas the binding site is concealed by further sialylation in healthy individuals. [166] Earlier study from our group has shown that PNA enhances both melanoma and colonic cancer cell growth and adhesion to endothelial cells, suggesting that PNA could act as a significant promotor in cancer metastasis. [167, 168]

PNA is not the major allergen responsible for peanut allergy. Allergy to peanut is usually lifelong and occurs in early age.[169] Peanut allergy is one of the most common food allergies and affects 2% of children in the UK. [170] The allergic
process is initiated with activation of immunoglobulin E involving a series of

functional and regulator proteins. Mammalian IgE provides the first barrier against pathogens. [171] [172, 173] There are two fundamental receptors for IgE, the high-affinity receptor for immunoglobulin E (FcεRI) and the low-affinity receptor CD23. [174] In the human body, FcεRI is initially expressed on the cell surface of mast cells, basophils, eosinophils, monocytes and Langerhans cells. [175-177] The binding site of FcεRI-IgE is located on the Fcε3 domain of IgE, and is mediated by cross-linking with galectin-3 acting as a secretory protein through their N-glycans. [178]

The binding of FcεRI to IgE activates its function and degranulates mast cell and basophils which plays an important effect in type I allergic reactions. [179] CD23 is a soluble calcium-dependent lectin and is expressed by B lymphocytes, monocytes and eosinophils. [180] CD23 acts as the promoter in cell growth of B lymphocytes, and synthesis of IgE. [181]

The PNA which in contrast to the peanut allergenic glycoproteins, Ara h1/2, is considered as a minor allergen, is reported to be involved in the Ig-binding complex. [182] Moreover, recent studies have showed that PNA-binding is a new marker for histiocytes which are specific cellular members of the immune system that participate in both immune and non-immune cellular reactions. [183]

PNA binds to the Thomsen-Friedenreich antigen

Previous studies have provided much epidemiological evidence of diet and colorectal cancer causation. [184] Previous studies have shown that lectins like PNA and galectins that bind to cancer cells such as human melanoma may cause increased metastasis. [185] Peanut (Arachis hypogaea) agglutinin, shows specific binding to beta-D-galactose residues, and has high affinity for the Gal (β1-3) GalNAc carbohydrate sequence which is also known as the Thomsen-Friedenreich antigen (TF antigen). As previously mentioned, TF antigen is expressed by the transmembrane mucin protein MUC1 which is overexpressed on cancer cell surface. [186] TF antigen is expressed in up to 90% of human cancers but is rarely expressed on healthy adult tissues.

The TF disaccharide is a core carbohydrate structure of O-linked oligosaccharides on glycoproteins. [187] It is normally concealed by glycosylation, sialylation or sulphation in the normal epithelium but becomes expressed in pre-malignant and cancerous epithelia in various sites. It behaves as an oncofetal antigen, expressed normally in the foetus then disappearing to be expressed again in hyperplasia or malignancy.

The increased expression of TF antigen is one of the commonest glycosylation changes in cancer and probably usually results from Golgi disarray resulting in a change in the site within the Golgi of expression of the β-galactosyl (l-3)-GalNac-α (2, 3) sialyl transferase. This could be a crucial early step in the development of colon cancer.
[188] In human melanoma the interaction between PNA and TF antigen occurs with high affinity and contributes to cell proliferation and differentiation. [165]

PNA induces cancer cell proliferation

Previous studies have showed that PNA has mitogenic effects on colon cancer cells, lymphocytes and on vascular smooth muscle cells. PNA at relevant concentrations achievable in vivo causes up to 50% increase in colon cell proliferation in vitro and, following peanut consumption, there was a similar (41%) increase in rectal mucosal proliferation in vivo in humans. Moreover, after ingestion of peanuts, there was a strong relationship between faecal hemagglutinating activity against TF-expressing desialylated red blood cells and rectal mitotic index. [160, 165]

In addition, when combined with epithelial growth factor (EGF), PNA and EGF caused maximal stimulation of proliferation much greater than either agent alone. This indicated that there might be possibilities for interactions between dietary lectins and endogenous growth-related peptide molecules in the colonic epithelium. [155] The mechanism of PNA-induced proliferation is unknown, but the apoptosis-inducing effects are dependent on internalization of the lectins. [166]

PNA as biomarker in cancer

Studies have shown that the effect of PNA on the cell surface is blocked by overexpressed sialic acid thus shielding its ligand. PNA agglutinates human erythrocytes only when the Neu5Ac on the cell surface of erythrocytes has been removed by prior neuraminidase (sialidase) treatment. PNA induced agglutination can be used as a marker for red blood cell polyagglutinability. PNA is also a T cell
mitogen. [189]

Binding between PNA and breast cancer cells is greater than PNA binding to normal cells, again due to increased expression of cancer specific TF antigen.
[190] PNA-binding has been widely studied as a tumour marker for several malignant cell types including the bladder tumour cells and hematopoietic cells.
[191] It has been shown that PNA predominately recognizes the galactosyl (β-1,3) N-acetyl-galactosamine (GalNAc) carbohydrate group which is commonly expressed as an O-linked glycan by tumour cells. [192] However it can also bind N- acetyllactosamine (LacNAc, Galβ1–4GlcNAc) with lower affinity than the TF antigen. [193]

PNA also interacts with the fibronectin isoform HFL-1 and has therefore been suggested as a potential marker for diagnosis and detection of rheumatic disease. [194] Previous studies have use fluorescein labelled PNA as a marker for both B cell and T cell differentiation. [195, 196] Tagged PNA has also been used as a chemiluminescence biomarker in breast cancer histochemistry. [197]

reference link :

Original Research:
“Appearance of peanut agglutinin in the blood circulation after peanut ingestion promotes endothelial secretion of metastasis-promoting cytokines” by Weikun Wang, Paulina Sindrewicz-Goral, Chen Chen, Carrie A Duckworth, David Mark Pritchard, Jonathan M Rhodes, Lu-Gang Yu. Carcinogenesis


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