Correspondence

Thromboxane Synthase and Organ Preference for Metastases

N Engl J Med 1993; 329:138-139July 8, 1993

Article

To the Editor:

Studies of the metastatic behavior of cancer suggest that one of the factors influencing the site at which tumor cells lodge is the presence of a special “soil” that favors the survival and growth of these tumor cells. A variety of hormonal and growth factors have been shown to influence the expansion of a metastatic colony.

One such factor is evidence that tumor cells and platelets interact to promote metastasis1. Tumor cells can activate platelets that undergo the release reaction and make available as yet unidentified mediators that promote tumor growth. In some models, the degree of platelet aggregation correlates with metastatic behavior1. One factor that may promote tumor growth is thromboxane A₂, the generation of which depends on thromboxane synthase activity. Thus, the “seeding” and growth of tumor cells in a particular organ may depend on its thromboxane synthase activity.

To evaluate this hypothesis, we correlated the distribution of metastases in patients with breast cancer from three large series2 with the thromboxane synthase content reported for some human tissues3. Breast cancer was chosen as the site of the primary cancer because it is a common tumor that metastasizes frequently to a variety of organs for which data on thromboxane synthase content are also available.

The correlation between the thromboxane synthase content of the various organs and the distribution of metastases is shown in Figure 1Figure 1Correlation between the Thromboxane Synthase Content of Individual Organs and the Distribution of Metastases from Breast Cancer.. The high correlation (r = 0.88, P<0.01) may explain why tumor cells have a specific affinity for certain organs.

There is both clinical and experimental support for a relation between thromboxanes and metastases. In a study involving breast cancer specimens from humans,4 Karmali et al. found high thromboxane B₂ levels associated with large tumors and lymph-node metastases. Similar results showing high thromboxane levels have been obtained with a highly metastasizing experimental reticulosarcoma5.

These data suggest that tumor cells lodge at sites with high capability for thromboxane synthesis. Whether this is a primary relation or a reflection of other mechanisms closely related to thromboxane metabolism remains unknown.

Amin A. Nanji, M.D.
New England Deaconess Hospital, Boston, MA 02215

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Citing Articles (8)

Citing Articles

1. 1

   Thibaut Dassesse, Xavier de Leval, Laurence de Leval, Bernard Pirotte, Vincent Castronovo, David Waltregny. (2006) Activation of the Thromboxane A2 Pathway in Human Prostate Cancer Correlates with Tumor Gleason Score and Pathologic Stage. European Urology 50:5, 1021-1031
   CrossRef

2. 2

   A. Giese, C. Hagel, E. L. Kim, S. Zapf, J. Djawaheri, M. E. Berens, M. Westphal. (1999) Thromboxane synthase regulates the migratory phenotype of human gliomacells. Neuro-Oncology 1:1, 3-13
   CrossRef

3. 3

   Kevin K Toller, James W Gigantelli, M.John Spalding. (1998) Bilateral orbital metastases from breast carcinoma. Ophthalmology 105:10, 1897-1901
   CrossRef

4. 4

   Yuji Soejima, Katsuhiko Yanaga, Takashi Nisizaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Keizo Sugimachi. (1998) Effect of thromboxane synthetase inhibitor on non-heart-beating donors in rat orthotopic liver transplantation. Surgery 123:1, 67-72
   CrossRef

5. 5

   Itsuo Yokoyama, Takaaki Kobayashi, Masataka Negita, Shuji Hayashi, Motohiko Yasutomi, Akio Katayama, Kazuharu Uchida, Hiroshi Takagi. (1996) Liberation of vasoactive substances and its prevention with thromboxane A2 synthase inhibitor in pig liver transplantation. Transplant International 9:1, 76-81
   CrossRef

6. 6

   Itsuo Yokoyama, Takaaki Kobayashi, Masataka Negita, Shuji Hayashi, Motohiko Yasutomi, Akio Katayama, Kazuharu Uchida, Hiroshi Takagi. (1996) Liberation of vasoactive substances and its prevention with thromboxane A ₂ synthase inhibitor in pig liver transplantation. Transplant International 9:1, 76-81
   CrossRef

7. 7

   Itsuo Yokoyama, Shuji Hayashi, Takaaki Kobayashi, Masataka Negita, Motohiko Yasutomi, Kazuharu Uchida, Hiroshi Takagi. (1995) Prevention of experimental hepatic metastasis with thromboxne synthase inhibitor. Research in Experimental Medicine 195:1, 209-215
   CrossRef

8. 8

   (1994) Correspondence and Short Communications. Acta Oncologica 33:6, 703-716
   CrossRef