- Mini Review
- Published:
Oncofetal antigen/immature laminin receptor protein in pregnancy and cancer
Cellular & Molecular Biology Letters volume 19, pages 393–406 (2014)
Abstract
The 37-kDa immature laminin receptor protein (iLRP) is a speciesconserved, universal immunogenic protein that is expressed in all thus-far examined embryonic and early fetal cells of inbred and outbred rodents. It has also been identified in human concepti. It is altered through normal maturation processes to become a non-immunogenic 67-kDa dimeric mature laminin receptor protein (mLRP) in mid-to late gestation in the mammalian fetus. This antigen ceases to be expressed as an active autoimmunogen in the full-term fetus and in the normal differentiating tissues and organs of the neonate or adult organism, apparently due to dimerization, but it is re-expressed as an immunogenic monomer in tumor cells. In this review, we highlight the known mechanisms of immune responses with particular emphasis on the possible role of the 37-kDa oncofetal antigen/immature laminin receptor (OFA/iLRP) in both pregnancy and cancer.
Abbreviations
- APC:
-
antigen processing cell
- CTL:
-
cytotoxic T lymphocyte
- DC:
-
dendritic cell
- DMBA:
-
2,4-dimethoxybenzaldehyde
- FasL:
-
Fas ligand
- Gal:
-
galectin
- IFN:
-
interferon
- IL:
-
interleuken
- iLRP:
-
immature laminin receptor protein
- MHC:
-
major histocompatibility complex
- mLRP:
-
mature laminin receptor protein
- NK:
-
natural killer
- OFA:
-
oncofetal antigen
- Tc:
-
T cytotoxic
- TCR:
-
T-cell receptor
- TGF:
-
transforming growth factor
- Th:
-
T helper
- TNF:
-
tumor necrosis factor
- Treg:
-
regulatory T cells
- Ts:
-
T suppressor
- TSTA:
-
tumor-specific transplantation antigen
References
Billingham, R.E., Brent, L. and Medawar, P.B. ‘Actively acquired tolerance’ of foreign cells. 1953. J. Immunol. 184 (2010) 5–8.
Billington, W.D. The immunological problem of pregnancy: 50 years with the hope of progress. A tribute to Peter Medawar. J. Reprod. Immunol. 60 (2003) 1–11.
Smith, T.R. and Kumar, V. Revival of CD8+ Treg-mediated suppression. Trends Immunol. 29 (2008) 337–342. DOI: 10.1016/j.it.2008.04.002.
Saito, S., Shiozaki, A., Sasaki, Y., Nakashima, A., Shima, T. and Ito, M. Regulatory T cells and regulatory natural killer (NK) cells play important roles in feto-maternal tolerance. Semin. Immunopathol. 29 (2007) 115–122. DOI: 10.1007/s00281-007-0067-2.
Wegmann, T.G, Lin, H., Guilbert, L. and Mosmann, T.R. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol. Today 14 (1993) 353–356.
Liu, F., Guo, J., Tian, T., Wang, H., Dong, F., Huang, H. and Dong, M. Placental trophoblasts shifted Th1/Th2 balance toward Th2 and inhibited Th17 immunity at fetomaternal interface. APMIS 119 (2011) 597–604. DOI: 10.1111/j.1600-0463. 2011. 02774.x.
Van Mourik, M.S., Macklon, N.S. and Heijnen, C.J. Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment. J. Leukoc. Biol. 85 (2009) 4–19.
Knutson, K.L. and Disis, M.L. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol. Immunother. 54 (2005) 721–728.
Blois, S.M., Kammerer, U., Alba Soto, C., Tometten, M.C., Shaikly, V., Barrientos, G., Jurd, R., Rukavina, D., Thomson, A.W., Klapp, B.F., Fernandez, N. and Arck, P.C. Dendritic cells: key to fetal tolerance? Biol. Reprod. 77 (2007) 590–598. DOI: 10.1095/biolreprod.107.060632.
Geissmann, F., Manz, M.G., Jung, S., Sieweke, M.H., Merad, M. and Ley, K. Development of monocytes, macrophages, and dendritic cells. Science 327 (2010) 656–661.
Nelson, D. and Ganss, R. Tumor growth or regression: powered by inflammation. J. Leukoc. Biol. 80 (2006) 685–690.
Zamarron, B. F. and Chen, W. Dual roles of immune cells and their factors in cancer development and progression. Int. J. Biol. Sci. 7 (2011) 651–658.
Steinman, R.M., Hawiger, D. and Nussenzweig, M.C. Tolerogenic dendritic cells. Annu Rev. Immunol. 21 (2003) 685–711.
Walker, M.R., Kasprowicz, D.J., Gersuk, V.H., Benard, A., Van Landeghen, M., Buckner, J.H. and Ziegler, S.F. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25-T cells. J. Clin. Invest. 112 (2003) 1437–1443.
Aluvihare, V.R., Kallikourdis, M. and Betz, A.G. Regulatory T cells mediate maternal tolerance to the fetus. Nat. Immunol. 5 (2004) 266–271. DOI: 10.1038/ni1037.
Zhao, J.X., Zeng, Y.Y. and Liu, Y. Fetal alloantigen is responsible for the expansion of the CD4(+)CD25(+) regulatory T-cell pool during pregnancy. J. Reprod. Immunol. 75 (2007) 71–81. DOI: 10.1016/j.jri.2007.06.05217.
Blois, S.M., Joachim, R., Kandil, J., Margni, R., Tometten, M., Klapp, B.F. and Arck, P.C. Depletion of CD8+ cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2 cytokine profile. J. Immunol. 172 (2004) 5893–5899.
Wang, H.Y. and Wang, R.F. Regulatory T cells and cancer. Curr. Opin. Immunol. 19 (2007) 217–223.
Rohrer, J.W. and Coggin, J.H., Jr. CD8 T-cell clones inhibit antitumor T-cell function by secreting IL-10. J. Immunol. 155 (1995) 5719–5727.
Rohrer, J.W., Culpepper, C., Barsoum A.L. and Coggin, J.H., Jr. Characterization of RFM mouse T lymphocyte anti-oncofetal antigen immunity in apparent tumor-free, long-term survivors of sublethal X-irradiation by limiting dilution T lymphocyte cloning. J. Immunol. 154 (1995) 2266–2280.
Rabinovich, G.A., Baum, L.G., Tinari, N., Paganelli, R., Natoli, C., Liu, F.T. and Iacobelli, S. Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response? Trends Immunol. 23 (2002) 313–220.
Cooper, D., Ilarregui, J.M., Pesoa, S,A., Croci, D.O., Perretti, M. and Rabinovich, G.A. Multiple functional targets of the immunoregulatory activity of galectin-1: Control of immune cell trafficking, dendritic cell physiology, and T-cell fate. Methods Enzymol. 480 (2010) 199–244. DOI: 10.1016/s0076-6879(10)80011-423.
Peng, W., Wang, H.Y., Miyahara, Y., Peng, G. and Wang, R.F. Tumorassociated galectin-3 modulates the function of tumor-reactive T cells. Cancer Res. 68 (2008) 7228–7236. DOI: 10.1158/0008-5472.can-08-124524.
Coggin, J.H. Jr., Barsoum, A.L. and Rohrer, J.W. 37-kiloDalton oncofetal antigen protein and immature laminin receptor protein are identical, universal T-cell inducing immunogens on primary rodent and human cancers. Anticancer Res. 19 (1999) 5535–5542.
Barsoum, A.L., Rohrer, J.W., Coggin, J.H., Jr. 37kDa Oncofetal antigen is an autoimmunogenic homologue of the 37kDa laminin receptor precursor. Cell. Mol. Biol. Lett. 5 (2000) 207–230.
Castronovo, V. Laminin receptors and laminin-binding proteins during tumor invasion and metastasis. Invasion Metastasis 13 (1993) 1–30.
Castronovo, V., Claysmith, A.P., Barker, K.T., Cioce, V., Krutzsch, H.C. and Sobel, M.E. Biosynthesis of the 67 kDa high affinity laminin receptor. Biochem. Biophys. Res. Commun. 177 (1991) 177–183.
Castronovo, V., Taraboletti, G. and Sobel, M.E. Functional domains of the 67-kDa laminin receptor precursor. J. Biol. Chem. 266 (1991) 20440–20446.
Coggin, J.H., Jr., Adkinson, L. and Anderson, N.G. Fetal antigens shared as transplantation rejection antigens on chemically induced mouse and hamster sarcomas. Cancer Res. 40 (1980) 1568–1573.
Rohrer, J.W., Rohrer, S.D., Barsoum, A. and Coggin, J.H., Jr. Differential recognition of murine tumor-associated oncofetal transplantation antigen and individually specific tumor transplantation antigens by syngeneic cloned BALB/c and RFM mouse T cells. J. Immunol. 152 (1994) 754–764.
Rohrer, J.W., Barsoum, A.L., Dyess, D.L., Tucker, J.A. and Coggin, J.H., Jr. Human breast carcinoma patients develop clonable oncofetal antigenspecific effector and regulatory T lymphocytes. J. Immunol. 162 (1999) 6880–6892.
Holtl, L., Zelle-Rieser, C., Gander, H., Papesh, C., Ramoner, R., Bartsch, G., Rogatsch, H., Barsoum, A.L., Coggin, J.H., Jr. and Thurnher, M. Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin. Cancer Res. 8 (2002) 3369–3376.
Friedrichs, B., Siegel, S., Kloess, M., Barsoum, A., Coggin, J., Jr., Rohrer, J., Jakob, I., Tiemann, M., Heidorn, K., Schulte, C., Kabelitz, D., Steinmann, J., Schmitz, N. and Zeis, M. Humoral immune responses against the immature laminin receptor protein show prognostic significance in patients with chronic lymphocytic leukemia. J. Immunol. 180 (2008) 6374–6384.
Payne, W.J., Jr. and Coggin, J.H., Jr. Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization. J. Nat. Cancer Inst. 75 (1985) 527–544.
Coggin, J.H., Jr. and Anderson, N.G. Cancer, differentiation and embryonic antigens: some central problems. Adv. Cancer Res. 19 (1974) 105–165.
Coggin, J.H., Jr., Rohrer, S.D., Hester, R.D., Barsoum, A.L., Rashid, H.U. and Gussack, G.S. 44-kd oncofetal transplantation antigen in rodent and human fetal cells. Implications of recrudescence in human and rodent cancers. Arch. Otolaryngol. Head Neck Surg. 119 (1993) 1257–1266.
Coggin, J.H., Jr. Embryonic antigens in malignancy and pregnancy: common denominators in immune regulation. Ciba Found. Symp. 96 (1983) 28–54.
Zhang, C., Duan, E., Cao, Y., Jiang, G. and Zeng, G. Effect of 32/67 kDa laminin-binding protein antibody on mouse embryo implantation. J. Reprod. Fertil. 119 (2000) 137–142.
Coggin, J.H., Jr. The implications of embryonic gene expression in neoplasia. Crit. Rev. Oncol. Hematol. 5 (1986) 37–55.
Chakravarty, P.K. and Sinha, D.K. Pregnancy induced mammary tumor specific effector cells are present long after parturition in a breast cancer model in rats. Cancer Letts. 154 (2000) 1–7.
Janerich, D.T. The fetal antigen hypothesis: cancers and beyond. Medical Hypotheses 56 (2001) 101–103. DOI: 10.1054/mehy.2000.1119.
Rohrer, S.D, Sarli, R.N., Barsoum, A.L, Hester, R.B. and Coggin, J.H., Jr. Expression of 44-kilodalton oncofetal antigen as a premalignancy marker in X irradiation-induced murine T-cell lymphoma. J. Nat. Cancer Inst. 84 (1992) 602–609.
Menard, S., Castronovo, V., Tagliabue, E. and Sobel, M.E. New insights into the metastasis-associated 67 kD laminin receptor. J. Cell. Biochem. 67 (1997) 155–165.
Gussack, G.S., Rohrer, S.D., Hester, R.B., Liu, P.I. and Coggin, J.H., Jr. Human squamous cell carcinoma lines express oncofetal 44-kD polypeptide defined by monoclonal antibody to mouse fetus. Cancer 62 (1988) 283–290.
Zelle-Rieser, C., Barsoum, A.L., Sallusto, F., Ramoner, R., Rohrer, J.W., Holtl, L., Bartsch, G., Coggin, J.H., Jr. and Thurnher, M. Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma. J. Urol. 165 (2001) 1705–1709.
Siegel, S., Wagner, A., Kabelitz, D., Marget, M., Coggin, J., Jr., Barsoum, A., Rohrer, J., Schmitz, N. and Zeis, M. Induction of cytotoxic T-cell responses against the oncofetal antigen-immature laminin receptor for the treatment of hematologic malignancies. Blood 102 (2003) 4416–4423. DOI: 10.1182/blood-2003-01-0198.
Siegel, S., Wagner, A., Friedrichs, B., Wendeler, A., Wendel, L., Kabelitz, D., Steinmann, J., Barsoum, A., Coggin, J., Rohrer, J., Dreger, P., Schmitz, N. and Zeis, M. Identification of HLA-A*0201-presented T-cell epitopes derived from the oncofetal antigen-immature laminin receptor protein in patients with hematological malignancies. J. Immunol. 176 (2006) 6935–6944.
Friedrichs, B., Siegel, S., Reimer, R., Barsoum, A., Coggin J., Jr., Kabelitz D., Heidorn, K., Schulte, C., Schmitz, N. and Zeis, M. High expression of the immature laminin receptor protein correlates with mutated IGVH status and predicts a favorable prognosis in chronic lymphocytic leukemia. Leuk. Res. 35 (2011) 721–729. DOI: 10.1016/j.leukres.2010.10.002.
Rohrer, J.W., Barsoum, A.L. and Coggin, J.H., Jr. Identification of oncofetal antigen/immature laminin receptor protein epitopes that activate BALB/c mouse OFA/iLRP-specific effector and regulatory T-cell clones. J. Immunol. 176 (2006) 2844–2856.
Barsoum, A.L., Liu, B., Rohrer, J.W., Coggin, J.H., Jr., Tucker, J.A., Pannell, L.K. and Schwarzenberger, P.O. Production, safety and antitumor efficacy of recombinant Oncofetal Antigen/immature laminin receptor protein. Biomaterials 30 (2009) 3091–3099. DOI: 10.1016/j.biomaterials.2009.02.022.
Coggin, J.H., Jr., Barsoum, A.L. and Rohrer, J.W. Tumors express both unique TSTA and crossprotective 44 kDa oncofetal antigen. Immunol. Today 19 (1998) 405–408.
Buto, S., Tagliabue, E., Ardini, E., Magnifico, A., Ghirelli, C., van den Brule, F., Castronovo, V., Colnaghi, M.I. and Sobel, M.E. Formation of the 67-kDa laminin receptor by acylation of the precursor. J. Cell. Biochem. 69 (1998) 244–251.
Karpatova, M., Tagliabue, E., Castronovo, V., Magnifico, A., Ardini, E., Morelli, D., Belotti, D., Colnaghi, M.I. and Menard, S. Shedding of the 67-kD laminin receptor by human cancer cells. J. Cell. Biochem. 60 (1996) 226–234.
Author information
Authors and Affiliations
Corresponding author
Additional information
In Memory of Professors Joseph H. Coggin and James W. Rohrer
Invited paper
Rights and permissions
About this article
Cite this article
Barsoum, A.L., Schwarzenberger, P.O. Oncofetal antigen/immature laminin receptor protein in pregnancy and cancer. Cell Mol Biol Lett 19, 393–406 (2014). https://doi.org/10.2478/s11658-014-0203-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11658-014-0203-7