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BCRL Home » History of the Breast Cancer Research Laboratory » Seminal work performed in the BCRL from 1972 to 1991

Seminal work performed in the BCRL from 1972 to 1991

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The MCF-7 cell as a model of human breast cancer in vitro

MCF-7 is a cell line established by Soule et al., derived from a pleural effusion from a patient with metastatic mammary carcinoma and has been maintained in the BCRL as well as other laboratories around the world for more than 30 years.

The inclusion of MCF-7 on this page has two purposes: first, as a tribute to the memory H. Soule who developed this cell line in 1970 at the Michigan Cancer Foundation, and second, to highlight important experiments performed in the BCRL that paved the way for further development and use of this cell line.

Since its initial description, MCF-7 has been verified both biochemically and cytologically as human. The demonstration of human alpha-lactalbumin and estrogen receptor protein in these cells support that its origin is in human breast tissue. The MCF-7 cell line contains receptor proteins specific for androgen, glucocorticoids and progesterone. It was initially observed, using light microscopy, that MCF-7 cells were comprised of polyhedral epithelial cells, a finding confirmed by scanning electron microscopy (Figure 1: Click to see).

Growth of MCF-7 cells in tridimensional matrix.

Various in vitro methods have been used to determine and characterize the malignant potential of tumor cells. MCF-7 cells cultured in a semisolid media like agar methocel, form colonies, and when seeded in a collagen matrix they form ball-like structures, or solid masses, of cells indistinguishable between those formed by primary breast cancer cells in vitro.

Another method used to test the growth properties of breast cancer cells has been their cultivation in collagen-coated cellulose sponges, providing an excellent technique for the study of three-dimensional expression of tumor morphology, and for investigations of MCF-7’s cellular interrelations. The morphologic pattern exhibited by the MCF-7 cells grown in the collagen-coated cellulose sponge was similar to the histological pattern found in both the antecedent primary tumor (Figure 2: Click to see) and the pleural metastasis from which this cell line was derived.

We demonstrated the importance of the hormonal milieu in the growing of MCF-7 cells in athymic mice. An important criterion of malignancy is the ability of transformed cells to grow in an adequate heterotransplantation system. Inmunologically depressed athymic mice (nu/nu) have the striking capability of discriminating between normal and neoplastic cells. Normal cells do not induce tumors, whereas malignant cells do.

The first experiment summarized in Table 1 demonstrated that MCF-7 cells were unable to grow in neither male nor female athymic mice. The gross examination of the area of cell inoculation and the histological study revealed a complete absence of the inoculated cells; only disorganization of the fat and some fibrosis were observed. Only those mice that received a transplant of pituitary glands or ovaries from syngenic mice induced the growth of MCF-7 cells (Table 1). Nine of the eleven (82%) inoculated female mice that received pituitary grafts developed palpable tumors within 12-18 days after inoculation. The tumors adhered to the skin and underlying muscle. No macroscopic metastatic growths were observed. Eight of the thirteen (61.5%) inoculated female mice that received ovary grafts developed palpable tumors within 12-18 days. No metastatic growths were observed. The tumors were small, oblong masses of 1.5-2.5 mm at their largest diameter. They adhered to the dermis of the skin and to the muscle of the abdominal wall. The tumors were firm, of a rubbery consistency, and presented resistance to sectioning. The tumor’s vascular bed was well developed. The area of the tumor was easily distinguished from the scar produced by the cauterization and the incision made during the transplant procedure. The histological pattern of the 17 tumors studied was identical. The tumors observed in mice isografted with pituitary glands or ovaries were indistinguishable.

Table 1 - Tumoral growth of human breast cancer cell line (MCF-7) in athymic mice

Group

Sex

Number of An.

Treatment

Number of An. withTumors/An
(%).

Latency in days

I*

Male

11

None

0/11
(0%)

-

II*

Female

12

None

0/12
(0%)

-

III*

Female

11

Pituitary isographs(1)

9/11
(82%)

12-18

IV*

Female

13

Ovary isographs(2)

8/13
(61.5%)

12-18

V**

Female

15

Estrogen  pellets(3)

12/15
(80%)

13-14

*    From : Russo, J., et al.  Tumoral growth of a human breast cancer cell line (MCF-7) in athymic mice.  III.  Int. Symp. on Detection and Prevention of Cancer, New York, (Herbert I. Mekseys, ed.),1976, pp. 617-626,
**  From: Russo, I. H. and Russo, J. Role of Pregnancy and Chorionic gonadotropin in breast cancer prevention. IV European Congress on Menopause (M. H. Birkhauser and H. Rozenbaum, Eds.) Editions Eska, Paris. 1998, pp133-142.

(1)Two pituitaries obtained from syngenic 60 days old female mice were grafted in the perirenal fat of each animal.
(2) Two ovaries obtained from syngenic 60 days old female mice were grafted in the perirenal fat of each animal.
(3)Each animal was implanted with a silastic tube containing 5mg of 17-b-estradiol in the interscapular region.
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The utilization of hormonal supplementation in the growth of MCF-7 cells in 1976 (Russo,J., McGrath,C.M., Russo,I.H. and Rich,M.A. Tumoral growth of a human breast cancer cell line (MCF-7) in athymic mice.  In: Nieburgs H.E.. (ed.), III Int.  Symp. on Detection and Prevention of Cancer, New York, 1976, pp. 617-626.), suggested the replacing the isografts by hormone pellets (Shafie, S.M., Giartham, F.H., Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic mice. J. Natl. Cancer Inst. 67:51-56, 1981).  We found out that the use of castrated male, estrogen supplemented, was also suitable for the growth of MCF 7 cells. The removal of the uterus and supplementation with estradiol either as pellets or silastic tube containing 5 mg of 17-b-estradiol in female mice is also a standard procedure.  The removal of the uterus avoids the swelling and accumulation of fluid in this organ due to the estrogenic stimulation.

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