| 51. |
- Sikut, R, et al.
(författare)
-
Distinct sub-populations of carcinoma-associated MUC1 mucins as detected by the monoclonal antibody 9H8 and antibodies against the sialyl-Lewis a and sialyl-Lewis x epitopes in the circulation of breast-cancer patients.
- 1996
-
Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 66:5, s. 617-23
-
Tidskriftsartikel (refereegranskat)abstract
- The cancer-associated epitope defined by the monoclonal antibody (MAb) 9H8 was shown to be closely related to the T antigen (Thomsen-Friedenreich antigen) by its sensitivity to 0-glycanase treatment of a mucin glycopeptide known to express this epitope. The reactivity with this glycopeptide increased upon neuraminiclase treatment, and among several MAbs tested for ability to block binding of the 9H8 antibody, the one specific for the T antigen was the most efficient. Out of 41 serum samples from breast-cancer patients, 11 showed elevated levels of the 9H8 epitope, and several sera also showed elevated levels of the cancer-associated carbohydrate epitopes sialyl-Lewis a and sialyl-Lewis x. By the use of antibodies specific for the MUC1 apoprotein (Ma552 and HMFG-2) it could be shown that these epitopes were attached to the MUC1 apoprotein in at least 4 of the cases. By combining antibodies specific to 9H8, sialyl-Lewis a and sialyl-Lewis x in catcher and tracer positions in several types of immunofluorometric assays, it was shown that the 9H8 epitope was rarely co-expressed with sialyl-Lewis a or sialyl-Lewis x epitopes an the same molecule, though all were expressed on MUC1 mucins. In fact, they can be considered as mutually exclusive epitopes, suggesting that these sera contained different populations of MUC1 mucins distinguishable by different sets of oligosaccharides. The existence of mutually exclusive carbohydrate epitopes on different MUC1 mucins in one and the same patient should be taken into account when designing immunoassays exploiting MUC1-reactive antibodies.
|
|
| 52. |
- Sikut, R, et al.
(författare)
-
Reactivity of antibodies with highly glycosylated MUC1 mucins from colon carcinoma cells and bile.
- 1998
-
Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - 1010-4283. ; 19 Suppl 1, s. 122-6
-
Tidskriftsartikel (refereegranskat)abstract
- The 55 antibodies submitted to the ISOBM TD-4 Workshop were analysed for their reactivity with core proteins of the heavily glycosylated MUC1 mucins from the colon carcinoma cell line COLO205 and bile. Both these mucins (designated as H-CanAg and SBG2) are highly glycosylated having 15 and 50 sugar residues per oligosaccharide, respectively. Only a few of the antibodies (129, 139, 153 and 162) reacted with both SBG2 and H-CanAg, and not with a control mucin (L-CanAg) having a similar glycosylation as H-CanAg. These antibodies were tested for their ability to catch soluble mucins, and the antibody 162 was found to be good also in this type of assay. The antibodies selected here should be useful for the detection of high glycosylated forms of the MUC1 mucin in tissues and serum.
|
|
| 53. |
|
|
| 54. |
- Yuan, XiMing, et al.
(författare)
-
The establishment of two cell lines from a mouse uterine cervical carcinoma (U14) and their metastatic phenotype changes
- 1995
-
Ingår i: Clinical and Experimental Metastasis. - 0262-0898 .- 1573-7276. ; 13:6, s. 463-73
-
Tidskriftsartikel (refereegranskat)abstract
- This paper studies the heterogeneity of metastatic potential of murine cervical carcinoma (U14). Two cell lines, P11-90 and L10-90, were established from a pulmonary metastatic substrain (U14AP11) and a lymphatic metastatic substrain (U14AL10), which were selected from U14 in vivo after 11 and 10 passages, respectively. The biologic differences between the two cell lines are as follows. (1) The cells of the P11-90 line grow more rapidly compared with the L10-90 line. From the 40th passage the medium pH was different. (2) The median number of chromosomes in P11-90 and L10-90 was 72 and 64, respectively; the rates of gap aberration were 88% and 78%, respectively. (3) The number of T lymphocytes and T helper lymphocytes in the peripheral blood from hosts with P11-90 were higher than that of hosts transplanted with L10-90, but the number of B lymphocytes in the latter was larger than that in the former. (4) The metastatic potential of each cell line partially decreased compared to the relative tumor substrain, but their organ preference still remained and the transplant locations, axillary or footpad, had a prominent influence on their metastatic behavior. To observe the effects of metastatic target organs on the metastatic phenotypes of tumor cells, as well as to explore a method for the establishment and maintenance of the metastatic organ preference of tumor cells, conditioned medium (CM) from pulmonary or lymphatic node diploid cells was added to the culture medium of P11-90 and L10-90. Two sublines, P + P11-90 and Ln + L10-90, were thus established. Using stereological methods we found that the majority of P + P11-90 cells became larger and their nuclei also increased in size compared with their parental lines, but the majority of Ln + L10-90 cells became smaller in size, though the nuclei were enlarged. The pulmonary metastatic rate and lymphatic metastatic rate of P + P11-90, as well as the lymphatic metastatic rate of Ln + L10-90, were restored dramatically. The results suggest that by taking advantage of the interaction between tumor cells and the CM of host cells the metastatic potential of tumor cell lines can be maintained in vitro. Our work may offer an experimental model for the manipulation of metastasis of cell lines coming from the same parent strain but with different metastatic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)
|
|
| 55. |
|
|
| 56. |
|
|
| 57. |
|
|
| 58. |
- Zhang, K, et al.
(författare)
-
A MUC1 mucin secreted from a colon carcinoma cell line inhibits target cell lysis by natural killer cells.
- 1997
-
Ingår i: Cellular immunology. - : Elsevier BV. - 0008-8749. ; 176:2, s. 158-65
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of two secreted mucin-type glycoproteins on natural killer (NK) cell cytotoxicity against K562 target cells has been studied. These mucins carry the carcinoma-associated sialyl-Lewis a carbohydrate epitopes and were purified from the human colon adenocarcinoma cell line COLO 205 secretions, where they lack their cytoplasmic parts. The larger one has an apoprotein encoded by the MUC1 gene, and the smaller one has CD43 (leukosialin) as the core protein. The purified MUC1 mucin could inhibit the target cell lysis by NK cells in a dose-response-dependent way, whereas other mucin domains of similar size showed no inhibition. The second mucin, CD43, inhibited lysis by NK cells, although less than the larger one. The MUC1 mucin bound to the enriched natural killer cell preparations in a partial Ca2+-dependent way as well. This mucin also bound to the target cells. The K562 cells, normally expressing high amount of CD43, showed an increased resistance to lysis by NK cells when transfected with MUC1 cDNA compared with nontransfected cells. One can speculate that mucins secreted or expressed in the plasma membrane of cancer cells could interfere with NK cell-mediated lysis.
|
|
| 59. |
- Zhang, K, et al.
(författare)
-
Comparison of sialyl-Lewis a-carrying CD43 and MUC1 mucins secreted from a colon carcinoma cell line for E-selectin binding and inhibition of leukocyte adhesion.
- 1997
-
Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - 1010-4283. ; 18:3, s. 175-87
-
Tidskriftsartikel (refereegranskat)abstract
- The colon carcinoma cell line COLO 205 has earlier been shown to express and secrete two mucin-type glycoproteins, the leukocyte-associated sialoglycoprotein CD43 or leukosialin (named L-CanAg) and the MUC1 mucin (named H-CanAg). Both glycoproteins carry sialyl-Lewis a epitopes and could bind transfected COS cells expressing E-selectin in a Ca(2+)- and E-selectin-dependent way. Using the monoclonal antibodies C50, C241 (both against sialyl-Lewis a), and CSLEX1 (against sialyl-Lewis x), the MUC1 mucin was shown to express both sialyl-Lewis a and sialyl-Lewis x epitopes, while the CD43 mucin expressed sialyl-Lewis a and almost no sialyl-Lewis x epitopes. These two secreted glycoproteins could inhibit human polymorphonuclear leukocyte or HL-60 cell adhesion to E-selectin-transfected COS cells or IL-1 beta-stimulated human endothelial cells in vitro. The inhibitory efficiency of the MUC1 mucin was 5-10 times larger than that of the CD43 mucin, when studied on endothelial cells and comparable amounts of sample were used. Removing the sialic acids from the MUC1 or CD43 mucins by sialidase treatment abolished the inhibitory effect. Monoclonal antibodies against sialyl-Lewis a greatly and equally inhibited the binding of the MUC1 or CD43 mucins, whereas an antibody against sialyl-Lewis x (CSLEX1) showed almost no inhibitory effect. The result proposes that the sialyl-Lewis a epitope on at least some mucin-type molecules bind E-selectin better than sialyl-Lewis x and that the potency of tumor-secreted mucins to interfere with leukocyte attachment to E-selectin could be dependent on the apoprotein size or its presentation of the carbohydrate epitopes.
|
|
| 60. |
- Zhang, K, et al.
(författare)
-
Secreted MUC1 mucins lacking their cytoplasmic part and carrying sialyl-Lewis a and x epitopes from a tumor cell line and sera of colon carcinoma patients can inhibit HL-60 leukocyte adhesion to E-selectin-expressing endothelial cells.
- 1996
-
Ingår i: Journal of cellular biochemistry. - 0730-2312. ; 60:4, s. 538-49
-
Tidskriftsartikel (refereegranskat)abstract
- A secreted MUC1 mucin from the spent medium of the colon carcinoma cell line COLO 205 carrying sialyl-Lewis a and x epitopes (H-CanAg) was purified by trichloroacetic acid precipitation and Superose 6 gel filtration. The purified H-CanAg inhibited adhesion of the leukocyte cell line HL-60 to E-selectin transfected COS-1 cells or interleukin-1 beta (IL-1 beta)-activated human umbilical vein endothelial cells. Sera from two patients with advanced colon carcinoma containing high concentrations of sialyl-Lewis a and x activity inhibited HL-60 cell adhesion to E-selectin-expressing COS-1 cells and IL-1 beta-activated endothelial cells. After affinity column absorption of the sialyl-Lewis a activity, the sera also lost most of their sialyl-Lewis x activity and at the same time their adhesion inhibitory effect. A large part of the sialyl-Lewis a/x activity in the two patients was found in fractions containing mucins having a MUC1 apoprotein, as shown by its size, and reactivity with the two anti-MUC1 apoprotein monoclonal antibodies, Ma552 and HMFG-2. The cell-adhesion inhibitory effect of the purified sialyl-Lewis a-carrying MUC1 mucin fraction from the sera of the two patients was stronger than that of smaller sized sialyl-Lewis a-carrying mucin-type glycoproteins also found in the patient sera. The MUC1 mucin fraction secreted by the COLO 205 cells and from the two sera were all shown to lack their C-terminal portion, in contrast to the MUC1 mucin from cells. It is hypothesized that sialyl-Lewis a- and/or x-containing mucins, especially MUC1, secreted by tumors can interact with E-selectin on endothelial cells and thus inhibit leukocyte adhesion.
|
|
