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Excerpt from The Trophoblast
and the Origins of Cancer:

One solution to the medical enigma of our time

Nicholas J. Gonzalez, MD and Linda L. Isaacs, MD

Part I: The Trophoblast as Metaphor for Cancer

Introduction

Over the past ten years, a number of cancer researchers have turned their attention to the non-malignant trophoblast, the embryonic tissue that develops into the mammalian placenta, the connection between the growing fetus in pregnancy and the maternal uterus. (1;2) Certainly, in its earliest incarnation as a relatively undifferentiated cell line capable of rapid proliferation, invasion into nearby tissues, migration, and new blood vessel formation, the trophoblast does resemble a typical aggressive neoplasm in its general behavior, and would seem to serve as an ideal model for the study of malignancy. Indeed, the similarities between cancer and trophoblast, as we continue to learn, go deep, right to the level of molecular mechanisms that define each of these two cell types, the one completely normal and necessary for human life, the other dreaded and deadly in its potential.

A recent article entitled “Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts” catalogues in elegant detail the biochemical pathways, the signaling and enzymatic processes shared by both trophoblasts and malignancy. (2) In the introduction of this 2007 publication, the authors summarize their thesis of a fundamental identity between the trophoblast and cancer ....

One hundred years earlier, long before the current resurgence of interest in the subject, in a series of long forgotten articles and in his 1911 book, The Enzyme Treatment of Cancer, the biologist Dr. John Beard working at the University of Edinburgh first proposed the trophoblast as the ideal model of cancer. (3) In his writings, Dr. Beard actually went quite a bit further than mere similarity between the two tissue lines, suggesting that the trophoblast not only resembled malignant tissue in its appearance and activity, but was the very cell line from which all cancer developed—and the only cell from which malignancy could form.

Beard claimed, as part of his trophoblast as cancer hypothesis, that nests of germ cells, the precursors in adults to gametes, remained scattered throughout all of our tissues, the remnants of their peculiar migration from the yolk sac to the developing gonads in the early embryo. Normally, such germ cells remain quiescent, but if stimulated into activity, they can develop as aberrant gametes, complete with their own trophoblast. Dr. Beard believed this “vagrant” trophoblast, growing out of place can, if unchecked, form malignancy.

Beard’s colleagues during his lifetime had little tolerance for his startling hypotheses, which they rejected out of hand as simply preposterous. When Beard died in 1924, he died in obscurity, his ideas about the trophoblast as the model for and actual origin of cancer long forgotten. But with the current growing interest among academicians who see in the trophoblast the ideal cancer analogy, we can think of no better time than the 150th anniversary of Dr. Beard’s birth to reassess his thesis from the perspective of contemporary molecular biology.


Reference List

1. Murray MJ, Lessey BA. Embryo implantation and tumor metastasis: common pathways of invasion and angiogenesis. Semin Reprod Endocrinol. 1999;17:275-290. PMID: 10797946

2. Ferretti C, Bruni L, Dangles-Marie V, Pecking AP, Bellet D. Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum Reprod Update. 2007;13:121-141. PMID: 17068222

3. Beard J. The Enzyme Treatment of Cancer. London: Chatto and Windus; 1911. Reprinted 2010 by New Spring Press.

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