(Last week I began a discussion of the unique properties and cancer-like behavior of embryonic trophoblast tissue. I conclude that discussion, with references, this week.)

In the early part of the twentieth century scientists began to notice a remarkable similarity between trophoblastic cells and cancer. It was said that if you mixed up microscope slides of both trophoblasts and cancer you could never again tell them apart. Both tumor tissue and trophoblast are highly proliferative, migratory and invasive, with an almost limitless ability to perpetuate themselves unless checked.

The main difference between cancer and trophoblast is that trophoblast's growth is a naturally self-contained process, limited to the environment of the uterus. In rare instances, however, trophoblast can escape from these natural boundaries, and the result is choriocarcinoma, a highly malignant form of cancer that is deadly unless treated by chemotherapy. In the vast majority of cases, the cancer-like growth of trophoblast is kept in check by a cascade of hormonal and cytokine signals.

Over the past several years there has been a stream of articles on the similarity between cancer and these trophoblastic cells of pregnancy. Here are excerpts from a few recent examples:

• "The metastatic properties of cancer may also have its counterpart in the migratory behavior of germ cells, and in the propensity of normal trophoblast cells to migrate to other organs...." L. Old, 2001
  
  
• "Extravillous trophoblast cells are...reminiscent of cancer cells." - F. M. Corvinus et al, 2003
  
  
• "Extravillous trophoblast cells resemble malignancies in their invasive and destructive features...." - T. G. Poehlmann et al., 2005
  
  
• "Trophoblast cells have remarkable growth and invasive properties in vivo, so much so that they resemble neoplastic cells...." Y.W. Loke in A. Moffett et al. 2006

In 2007, Dominique Bellet and her Parisian colleagues conducted a comprehensive review of the points of resemblance between trophoblast and cancer at the molecular level. They remarked on the "striking similarities between the proliferative, migratory and invasive properties of placental cells and those of cancer cells." (Ferretti et al 2007)

The many similarities of cancer and trophoblast have profound implications for both our understanding of the natural history of cancer and for its treatment. I find it sad that, with a few notable exceptions, such as Dr. Lloyd J. Old of Memorial Sloan-Kettering Cancer Center, most authors in the field remain unaware of the work of John Beard, DSc. Beard was a British scientist who, 100 years ago, wrote a series of journal articles and a popular book on the similarity of trophoblast to cancer. Beard was convinced that cancer was in fact trophoblast, the outgrowth in every instance of an aberrant germ cell.

At one time, Beard was taken quite seriously, For example, the celebrated Sir William Osler lauded Beard's work in embryology, and the New York Times said: "His utterances in regard to matters within his scientific domain are authoritative and universally regarded as final." Beard advocated, as the practical corollary of his theory, the use of intravenous pancreatic enzymes in cancer treatment. A great many physicians began using Beard's treatment. However, Beard's therapeutic hypothesis was eventually abandoned, possibly because of the fact that the various enzyme preparations available in those days were uneven in quality and easily destroyed by mishandling, and thus produced extremely inconsistent results. Today, Beard doesn't even merit an entry in Wikipedia. Next year, however, is the sesquicentenary of his birth. Given the growing interest in the similarity of cancer and trophoblast, this might be an opportune moment for scientists to take a fresh look at John Beard's thinking on this still largely unexplored subject.

--Ralph W. Moss, Ph.D.

References:

Corvinus FM, Fitzgerald JS, Friedrich K, Markert UR. Evidence for a correlation between trophoblast invasiveness and STAT3 activity. Am J Reprod Immunol. 2003 Oct;50(4):316-21.

Ferretti C, Bruini 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.

Niederhuber JE. Developmental biology, self-renewal, and cancer. Lancet Oncol. 2007;8:456-457.

Moffett A, Loke C, McLaren A, Eds. Biology and Pathology of Trophoblast. Cambridge: Cambridge University Press, 2006.

Old LJ. Cancer/Testis (CT) antigens - a new link between gametogenesis and cancer. Cancer Immunity 2001;1:1.

Poehlmann TG, Fitzgerald JS, Meissner, et al. Trophoblast invasion: tuning through LIF, signalling via Stat3. Placenta. 2005;26 Suppl A:S37-41.

Richardson MA and Narraway J. A treasure house of comparative embryology. Int J Dev Biol. 1999;43:591-602.

Young, Maureen. What is Baby Expecting: How we are Fed to Grow Before We are Born. Maureen Young (publisher), 2001.

For information on Osaka City placenta disposal:
http://www.city.osaka.jp/kankyojigyo/english/waste/pets.html

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