The use of radioiodinated alpha-fetoprotein for the scintigraphic detection of mouse mammary carcinomas

Specific cytoplasmic alpha-fetoprotein binding protein in MCF-7 human breast cancer cells and primary breast cancer tissue

“…Taken together, previously reported evidence for de novo synthesis of free immunoreactive and bound non-immunoreactive forms of cytoplasmic AFP by MCF-7 cells [5] and the present evidence for the existence of cytoplasmic AFP-receptors in these same cells is consistent with the conclusion that most of the endogenous AFP synthesized in breast cancer cells is rapidly bound by hydrophobic binding to specific cytoplasmic AFP-receptors, and that binding of AFP to these receptors apparently masks its immunoreactivity. In contrast to previously reported evidence for an endogenous origin of AFP in breast cancer cells [5], cell surface membrane AFP-receptors have been detected on spontaneous mouse mammary neoplasms and MCF-7 human breast cancer cells which mediate rapid internalization of exogenous AFP [4,6,7,8]. The binding parameters reported for MCF-7 cells [8] were interpreted to indicate that two populations of cell surface AFP-binding sites were present, with apparent Kd's of 4.5 x 10-9M (2000 sites per cell) and of 1.3 x 10-SM (135,000 sites per celt) respectively.…”

“…In our initial studies, markedly increased amounts of previously undetected nonimmunoreactive AFP which became immunoreactive after treatment with 0.4 M KC1 was detected and measured in primary human breast cancer tissue cytosol [3], and subsequently biosynthesis of free and bound forms of endogenous AFP were demonstrated in MCF-7 human breast cancer cells [5]. In a different approach, spontaneous mouse mammary neoplasms [4,6] and MCF-7…”

Increased Alpha-Fetoprotein Receptor in the Serum of Patients with Early-Stage Breast Cancer

“…In vitro and in vivo studies showed that malignant cells regain the ability to take up afp via a receptor that would be present in undifferentiated cells of either embryonic or tumour origin [10][11][12][13][14][15] , but mostly absent in normal adult cells. The existence of such a receptor for afp (recaf) was then demonstrated and functionally characterized in several cell lines [16][17][18] .…”

Monoclonal Antibodies Directed against a Widespread Oncofetal Antigen: The Alpha-Fetoprotein Receptor

“…Alpha-fetoprotein (AFP), the most abun dant plasma protein during fetal life, has been found in the cytoplasm of neuroblasts and other embryonic tissues not involved in the production and secretion of this protein [1][2][3][4][5][6][7], The presence of intracellular AFP in these tissues has been shown to be mostly due to uptake from the extracellular milieu [8][9][10][11][12][13][14][15][16][17] via a previously postulated receptor-mediated mechanism [5] tionship between AFP uptake and cell differ entiation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] suggested that malignant cells might reexpress the AFP receptor as they dedifferentiate, a behavior observed for a number of different proteins (oncofetal anti gens) and metabolic pathways [18], The up take of AFP by cancer cells was subsequently confirmed both in vitro [19][20][21] and in vivo [22,23], Direct evidence for the presence of an AFP receptor on malignant cells has been obtained from Scatchard analysis using the MCF-7 human mammary carcinoma cell line [24] and the murine YAC-1 lymphoma cell line …”

“…This strategy, which proved useful for tumor scin tigraphy [22,23], has, however, some impor tant drawbacks: First, there is the practical difficulty in obtaining significant amounts of pure and active human AFP. Second, the affinity of AFP towards its receptor is rela tively low [24,25].…”