Abstract
In some epithelial cells studied in vitro a membrane-bound folate receptor initiates the process for cell accumulation of 5-methyltetrahydrofolic acid. This receptor was found to be GP38, an overexpressed, glycosyl-phosphatidylinositol anchored glycoprotein, recognized by two monoclonal antibodies, designated MOv18 and MOv19. Using immunoblotting with MOv19, radioimmunoassay with MOv18 and 19, Northern blot analysis, and radioligand binding when possible, we describe the limited expression of the folate receptor in a large number of normal tissues from four autopsies. The immunoblot technique detected as little as 40 pg (≈1 fmol) of receptor protein. Choroid plexus consistently had the largest amount of folate receptor. Other tissues containing substantial amounts of receptor included lung, thyroid, and kidney. The liver, intestines, muscle, cerebellum, cerebrum, and spinal cord were immunologically nonreactive. Folate receptor gene expression determined by Northern blot analysis confirmed these observations. We also show that several malignant cell lines express significantly more receptor than normal epithelial cells or fibroblasts. Specifically, malignant cells bound ≥20 pmol [3H]folate/106 cells, while normal epithelial cells and fibroblasts bound ≤1 pmol radioligand/106 cells. We also demonstrate that 4 of 6 brain tumors overexpress the folate receptor. These studies reveal the limited normal tissue distribution of the folate receptor, a cell surface protein which may be a useful immunological or pharmacological target for the development of selective cancer therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3396-3401 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 52 |
| Issue number | 12 |
| State | Published - Jun 15 1992 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. / Weitman, Steven D; Lark, Richard H.; Coney, Leslie R.; Fort, Daniel W.; Frasca, Verna; Zurawski, Vincent R.; Kamen, Barton A.
In: Cancer Research, Vol. 52, No. 12, 15.06.1992, p. 3396-3401.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues
AU - Weitman, Steven D
AU - Lark, Richard H.
AU - Coney, Leslie R.
AU - Fort, Daniel W.
AU - Frasca, Verna
AU - Zurawski, Vincent R.
AU - Kamen, Barton A.
PY - 1992/6/15
Y1 - 1992/6/15
N2 - In some epithelial cells studied in vitro a membrane-bound folate receptor initiates the process for cell accumulation of 5-methyltetrahydrofolic acid. This receptor was found to be GP38, an overexpressed, glycosyl-phosphatidylinositol anchored glycoprotein, recognized by two monoclonal antibodies, designated MOv18 and MOv19. Using immunoblotting with MOv19, radioimmunoassay with MOv18 and 19, Northern blot analysis, and radioligand binding when possible, we describe the limited expression of the folate receptor in a large number of normal tissues from four autopsies. The immunoblot technique detected as little as 40 pg (≈1 fmol) of receptor protein. Choroid plexus consistently had the largest amount of folate receptor. Other tissues containing substantial amounts of receptor included lung, thyroid, and kidney. The liver, intestines, muscle, cerebellum, cerebrum, and spinal cord were immunologically nonreactive. Folate receptor gene expression determined by Northern blot analysis confirmed these observations. We also show that several malignant cell lines express significantly more receptor than normal epithelial cells or fibroblasts. Specifically, malignant cells bound ≥20 pmol [3H]folate/106 cells, while normal epithelial cells and fibroblasts bound ≤1 pmol radioligand/106 cells. We also demonstrate that 4 of 6 brain tumors overexpress the folate receptor. These studies reveal the limited normal tissue distribution of the folate receptor, a cell surface protein which may be a useful immunological or pharmacological target for the development of selective cancer therapy.
AB - In some epithelial cells studied in vitro a membrane-bound folate receptor initiates the process for cell accumulation of 5-methyltetrahydrofolic acid. This receptor was found to be GP38, an overexpressed, glycosyl-phosphatidylinositol anchored glycoprotein, recognized by two monoclonal antibodies, designated MOv18 and MOv19. Using immunoblotting with MOv19, radioimmunoassay with MOv18 and 19, Northern blot analysis, and radioligand binding when possible, we describe the limited expression of the folate receptor in a large number of normal tissues from four autopsies. The immunoblot technique detected as little as 40 pg (≈1 fmol) of receptor protein. Choroid plexus consistently had the largest amount of folate receptor. Other tissues containing substantial amounts of receptor included lung, thyroid, and kidney. The liver, intestines, muscle, cerebellum, cerebrum, and spinal cord were immunologically nonreactive. Folate receptor gene expression determined by Northern blot analysis confirmed these observations. We also show that several malignant cell lines express significantly more receptor than normal epithelial cells or fibroblasts. Specifically, malignant cells bound ≥20 pmol [3H]folate/106 cells, while normal epithelial cells and fibroblasts bound ≤1 pmol radioligand/106 cells. We also demonstrate that 4 of 6 brain tumors overexpress the folate receptor. These studies reveal the limited normal tissue distribution of the folate receptor, a cell surface protein which may be a useful immunological or pharmacological target for the development of selective cancer therapy.
UR - http://www.scopus.com/inward/record.url?scp=0026752798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026752798&partnerID=8YFLogxK
M3 - Article
C2 - 1596899
AN - SCOPUS:0026752798
VL - 52
SP - 3396
EP - 3401
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 12
ER -