The potential role of integrin receptor subunits in the formation of local recurrence and distant metastasis by mouse breast cancer cells.
BACKGROUND
The mechanisms by which surgical injury fosters tumor growth are examined.


METHODS
TA3Ha mouse breast tumor line and its subline (TA3AD) differing in their metastatic abilities as tested by two models were used. In model a, TA3Ha/TA3AD tumors were grown in the mammary fat pads of mice and then surgically removed with a curative intent. In model b, TA3Ha/TA3AD cells were injected intravenously into mice subjected to liver or spleen wedge resection. Frequency of tumor formation at various sites was assessed. Expression of integrin, immunoglobulin, and proteoglycan cell adhesion receptors on TA3Ha and TA3AD cells was examined by flow cytometry. The roles of these receptors in metastasis were examined by blocking them by selected ligands and/or antibodies.


RESULTS
Frequencies of local recurrence and axillary metastasis after surgical resection, were 43% (32/74), and 37% (27/74) with TA3Ha tumors and 4% (1/29) at both sites with TA3AD tumors. Tumors at surgically injured spleen and the liver were seen in 75% (141/189) and 45% (107/240) of the mice with TA3Ha cells and in 8% (3/38) and 10% (4/42) of the mice with TA3AD cells. alpha 5 and CD44 receptors were expressed by TA3Ha cells but not by TA3AD cells. Other receptors examined were similarly expressed by both cell lines. Blocking of alpha 5 receptor by fibronectin reduced tumor implantation in a dose-dependent manner.


CONCLUSIONS
The data suggest a correlation among the ability to implant at surgically injured sites, to form local recurrence, and to express the fibronectin receptor subunit.
Department of Surgery, Evanston Hospital, IL 60201, USA.
M S
MS
Murthy
S E
SE
Reid
X F
XF
Yang
E P
EP
Scanlon
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016023:Integrins / Q000502:physiology*; D008099:Liver / Q000601:surgery; D008207:Lymphatic Metastasis / Q000503:physiopathology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology; D009364:Neoplasm Recurrence, Local / Q000503:physiopathology*; D009366:Neoplasm Seeding; D016024:Receptors, Cytoadhesin / Q000096:biosynthesis; D013154:Spleen / Q000601:surgery; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013997:Time Factors
D016023:Integrins; D009363:Neoplasm Proteins; D016024:Receptors, Cytoadhesin