It's common wisdom that babies breast-fed on mother'smilk have fewer sniffles, coughs and pneumonias thaninfants nourished by formula out of a bottle. Exactly hownatural human milk works this anti-bacterial magic is stillthe subject of research.

One such study began in the mid-1980s at the Universityof Lund, Sweden. After reconfirming that indeed breast-fed children have a lower incidence of respiratoryinfections than bottle babies, the investigators went afterthe anti-bacterial factor involved.

Lund immunologist Anders HKansson recalls that onetarget marker was bacterial adherence. "If bacteria canadhere to the respiratory tract," he told BioWorld Today,"that might lead to infection. So we were looking forsome kind of anti-adhesive capacity in the milk."

At first, the researchers scraped surface cells from theirown throats and put them in human milk together withthe pathogens, to see if the milk could block the binding.

Later, they added viruses to their system, to observe viral-bacterial interaction. At that point, HKansson said, "wethought we should have a cell that is more homogeneousall the time, and that lives long enough to do a viralinfection first, then study bacterial adherence. So theyswitched to a human lung-cancer cell line, which filledthat bill.

Milk Packs Apoptosis Weapon

"After introducing milk," he continued, "when I looked atthose tumor cells, they looked very very funny; they weredying of apoptosis."

This unexpected observation led HKansson and hiscolleagues to conduct an all-out search for the apparentantitumor agent hidden in mother's milk. Theirpreliminary finding appears in the current Proceedings ofthe National Academy of Sciences, (PNAS), dated Aug.15, 1995. Its title: "Apoptosis induced by a human milkprotein."

That protein was a-lactalbumin, a principal component ofhuman milk _ but with a difference. Instead of the 14-kiloDalton, 123-amino acid molecule of monomeric a-lactalbumin, the version of the protein that killed "funny-looking" cancer cells turned out to be multimeric _ anaggregation of two (dimeric), three (trimeric) and up tosix (hexameric) monomers.

Besides gifting newborns with muscle mass and fat, milkis well known as a purveyor of antibodies and otherimmune-system elements to shield nursing babies fromlife's infectious germs. Also, rumors circulate inscientific circles that mother's milk protects againstcancer.

"Human milk from several donors," Lund's PNAS paperreported, "induced apoptosis in transformed andnontransformed immature cell lines and lymphoid cells,but not in mature cells."

It also pointed out that "The factors that regulate theaggregation state of a-lactalbumin in whole human milkare not understood . . . multimers of a-lactalbumin occurnaturally."

HKansson's extracted a-lactalbumin monomer did notaggregate spontaneously into apoptosis-wieldingmultimeric proteins in vitro. "Passaged over an ion-exchange column," he said, "it multimerized and becamecytotoxic."

The multimers wreaked apoptotic death on lung cancercells and rat thymocytes, by inducing a concentration-dependent increase in calcium ions. Removing calciumprevented cell death.

"What we are doing at the moment," HKansson said, "istrying to characterize what is happening, trying to seewhat this protein is binding to, what is happening withinthe cell; what kind of cell signaling is taking place."

Moving from these in vitro inquiries to in vivo animalstudies "will take a couple of weeks or months to getstarted," he observed, adding "We're on the edge of doingso."

He said, "We haven't really designed the experiment yet;I guess we will see if we can treat mice with tumors."

Still in hot pursuit of the underlying anti-cancermechanism, he and his co-authors have formed ahypothesis: "We see," he said, "that immature cells, andcancer cells _ which have an immature phenotype _ arethe only ones affected by the multimer. And that couldmean that milk, during the neonatal period, could help indeveloping the mucosal lining of the gastrointestinaltract. That tissue is not fully developed at birth," heobserved. "It takes another three or four months beforeyou have a good barrier."

His paper concludes that "analysis of the mechanism bywhich multimeric a-lactalbumin induces apoptosis intransformed epithelial cells could lead to the design ofantitumor agents." But HKansson himself said: "Don'tcall it an antitumor effect," he said, "but some sort ofdevelopment factor, which takes away immature cells infavor of more mature cells, so the epithelium woulddevelop much faster."

He added, "And the by-effects will be also taking awaycancer cells of immature type."

Thinking About A Potential Drug

As for a potential anti-cancer therapeutic, "I have noplans yet," HKansson said. "These are just verypreliminary results. But we do have to start thinkingabout what to do with them."

Molecular biologist Alan Colman is research director ofPPL Therapeutics, a Scottish biotech firm that pioneeredproduction of useful proteins in the mammary glands ofsheep.

PPL, he told BioWorld Today, "has a major program witha multinational partner, to overexpress a-lactalbumin inlivestock for nutritional purposes."

Colman finds "very interesting HKansson's observationthat when exposed to multimeric a-lactalbumin, tumorcells keel over and die." But he wondered: "How solid ishis hypothesis that in the infant gut [the multimericprotein] can modify cells?" n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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