L1CAMgene and injecting them into
mice, the cells behaved far differently
than unaltered controls. When normal
cancer cells are injected, “it will form
only a local tumor, but now that there
is L1, it will metastasize to the liver,”
Ben-Ze’ev says. Furthermore, when
the researchers looked for L1CAM in
colorectal tumor samples from patients,
they found it—not in all the cells, but in
those at the invasive edge, leading the
charge of the cancer’s spread. “What was
really surprising to me is that a gene...
can so dramatically reprogram the prop-
erties of an already tumorigenic cell to
form [a] metastasis,” Ben-Ze’ev recalls
(J Cell Biol, 168:633–42, 2005).
Research groups have since found
that L1CAM is associated with metas-
tasis in a variety of cancers, and anti-
bodies against the protein have been
tested as cancer therapies in mice with
some success. Recently, Karuna Ganesh
of Memorial Sloan Kettering Can-
cer Center (MSKCC) in New York and
her colleagues took a new approach to
further investigate how L1CAM con-
fers metastatic powers on cancer cells.
Ganesh, who is a practicing oncologist as
well as a researcher, explains that while
tumors that remain localized are usu-
ally treatable, cancers that have metas-
tasized are far more deadly and difficult
to treat. Indeed, the vast majority of
cancer deaths are from metastatic can-
cer. “Something is fundamentally differ-
ent about the biology of these metastatic
tumors that makes them so impossible to
treat, and this is really a pressing clini-
cal need, to find better ways of attacking
metastatic disease,” Ganesh says.
With that need in mind, in 2014
Ganesh joined the lab of MSKCC
metastasis researcher Joan Massagué,
where she worked to harness what was
then a brand-new model for studyingcancer: tumor organoids, tiny three-
dimensional models grown in a dish
using tumor samples that were removed
from patients. (See “Treatment in 3-D,”
The Scientist, July/August 2019.) Look-
ing in these models for the factors that
distinguished metastasizing cells from
tumor cells that stayed put, Ganesh and
her colleagues came across L1CAM. Con-
sistent with Ben-Ze’ev’s findings from a
decade before, metastasis-initiating cells
had lots of the protein, while other can-
cer cells didn’t.Something is fundamentally
differ ent about the biology
of these metastatic tumors
that makes them so impossible
to treat.
—Karuna Ganesh
Memorial Sloan Ketter ing Cancer Center