Endogenous immune response to gangliosides in patients with confined prostate cancer

Abstract

Our study investigated whether endogenous IgM antibodies to gangliosides occur in patients with early stages of prostate cancer (CaP) patients, after defining ganglioside profiles of CaP cell lines. Immune and resorcinol staining detected the presence of gangliosides GM3, GM2, GD3, GD2 and GD1a but not GM1a, GD1b or GT1b in the extracts of normal prostatic epithelial cells (PrEC) and neoplastic androgen‐insensitive (PC‐3, DU145) and ‐sensitive (LNCaP‐FGC and LNCaP‐FGC‐10) CaP cells. Using a sensitive ELISA, developed and validated in our laboratory, the titers of IgM against 8 gangliosides from sera of patients with benign prostatic hyperplasia (BPH) (n = 11), organ‐confined (T1/T2, n = 36) and unconfined (T3/T4, n = 27) CaP and age‐matched healthy men (n = 11) were determined double‐blinded. Using ANOVA and Fisher's least significant difference (LSD) methods, the log‐titers among different groups were compared. CaP patients differed from healthy and BPH patients in increased titers against GD1a and decreased titers against GD3. Titers of antibodies to other gangliosides exhibited no difference between CaP patients and others. The specific augmentation of anti‐GD1a IgM in patients with organ‐confined CaP (stage T1/T2) but not in patients with unconfined CaP (stage T3/T4) or BPH or in healthy controls is striking. This finding together with identification of GD1a as a major ganglioside in CaP cell lines and with the accruing studies on the immunosuppressive nature of GD1a indicates that augmentation of anti‐GD1a IgM in confined CaP may signify an early endogenous immune response to eliminate a “danger signal” from tumor microenvironment and circulation. © 2005 Wiley‐Liss, Inc.

Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling

“…We also tried to detect a small change of cell surface gangliosides by FACS analysis with antibodies against GD1a, GM2, GM1 (Seikagaku Biobusiness, Tokyo, Japan) and GD2 (Upstate, Lake Placid, NY, USA), as a previous report suggested possible existence of these gangliosides in the cells. 22 However, all the antibodies failed to detect any significant change in either NEU3 overexpressing or silencing cells (data not shown).…”

Efficient eradication of hormone‐resistant human prostate cancers by inactivated Sendai virus particle

“…32 However, when the cell surface gangliosides within prostate epithelium was precisely examined, GD1a gangliosides were found to be the most prevalent gangliosides among prostate cancer cell lines, including PC3 and DU145, whereas GD1a gangliosides were barely detectable in both hormone-sensitive prostate cancer LNCap cells and normal prostate epithelium using thin-layer chromatography. 43,44 Furthermore, when we determined the quantity of gangliosides in prostate cancer cell lines using HPLC, we found that SPG, another receptor for HVJ, also increased in hormonerefractory prostate cancer cells as well as GD1a. The total amount of GD1a and SPG was much higher in PC3 and DU145 than LNCap and PNT2 (Fig.…”

“…43 Ganglioside GD1a is synthesized from GM1a by a 2,3 sialyltransferase (ST3Gal) I and/or II. 45 RT-PCR analysis showed that the expression of ST3Gal I was much higher in PC3 cells than in LNCap and PNT2 (data not shown).…”

“…The observed specificity of cell fusion in PC3 and DU145 cells upon exposure to HVJ-E is likely because of the expression of GD1a, a receptor for HVJ, which predominates in hormone-resistant prostate cancer cells. 43,44 Because fused cells stop dividing and became apoptotic, selective fusion of cancer cells may contribute to the anti-tumor effects of HVJ-E, in addition to the tumor killing activity of IFN secretion as well as the induction of anti-tumor immunity.…”

Gangliosides and Antigangliosides in Malignant Melanoma

“…In patients with thyroid cancer well differentiated, the level of anti-GM1 IgG and IgM type was associated with carcinogenesis, with no diagnose value in thyroid cancer [120,121,122]. In a big cohort of patients with lupus systemic erythematous the presence of both anti-GM1 IgM and IgG type were associated with neuro-psychiatric disorders and depression.…”