Muscarinic receptors autoantibodies purified from mammary adenocarcinoma-bearing mice sera stimulate tumor progression.
The ability of tumor cells to stimulate adaptive immunity, particularly by inducing anti-tumor antibodies (Abs), has been extensively reviewed. LM3 is a tumorigenic cell line derived from a murine mammary metastatic adenocarcinoma that spontaneously overexpressed mAchR. Here we investigate the ability of Abs purified from the sera of LM3 tumor-bearing mice, directed against muscarinic acetylcholine receptors (mAchR) to modulate tumor cells' proliferation and angiogenesis. We observed that IgG from early tumor bearers (ETB), 14-day LM3 tumor, and from late tumor bearers (LTB), 28-day LM3 tumor, displaced tritiated quinuclidinyl benzilate binding to LM3 tumor cells, confirming Abs interaction with cholinoceptors, while IgG from normal mice did not modify the antagonist binding to mAchR at any concentration tested. In addition, Abs from ETB and LTB immunoblotted a protein of 70 kDa on murine tumor cells and on heart homogenates that was also recognized by a specific anti-M(2) receptor monoclonal antibody. We also observed that IgG purified from ETB-stimulated LM3 cells' proliferation in a more effective manner than the muscarinic agonist carbachol (CARB) did. IgG from LTB-potentiated LM3 cells induced angiogenesis by increasing the number of blood vessels and VEGF-A production in peritumoral skin "via" mAchR, in an agonist similar manner. All effects were blocked by preincubating cells with the non-selective antagonist atropine. In conclusion, autoAbs purified from LM3 tumor-bearing mice sera exert different pro-tumor actions depending on the stage of tumor development: in ETB, they stimulate tumor cells' proliferation, while in LTB they potentiate tumor neovascularization.
Fiszman
Gabriel
G
Area Investigación, Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Av. San Martín 5481, CP 1417, Buenos Aires, Argentina.
Cattaneo
Valentina
V
de la Torre
Eulalia
E
Español
Alejandro
A
Colombo
Lucas
L
Sacerdote de Lustig
Eugenia
E
Sales
María Elena
ME
D000230:Adenocarcinoma / Q000097:blood* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000097:blood* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000276:immunology* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001323:Autoantibodies; D007074:Immunoglobulin G; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D042461:Vascular Endothelial Growth Factor A; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D002217:Carbachol; D013936:Thymidine