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Survival Niche for Cancer Cells

Cancer cells do not grow equally well everywhere in the body. Often, they first create the conditions in which they can grow. Many years ago researchers discovered that solid tumors attract blood vessels to ensure their supply of nutrients by secreting specific factors. Now the immunologist Dr. Uta Höpken (Tumor and Immunogenetics Research Group at the Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch in the Helmholtz Association) and the hematologist Dr. Armin Rehm (Charité – Virchow-Klinikum, Department of Hematology, Oncology and Tumor Immunology, MDC) have shown for the first time that specific forms of lymphoma also create their own survival niche (Blood, doi:10.1182/blood-2010-11-321265)*.

Lymphoma is
the term used to describe a group of cancers of the lymphatic system. Lymphoma
cells are abnormal immune cells (B cells or T cells), a specific group of white
blood cells (lymphocytes). Using a mouse model, Dr. Rehm and Dr. Höpken
demonstrated for the first time that the dissemination of lymphoma cells and
their accumulation in the lymph nodes or spleen is dependent on specific
signaling or growth substances, the chemokines CCL19 or CCL21.

normally attract immune cells to a site of infection or inflammation. As former
immune cells, lymphoma cells have special antennas (receptors) on their cell
surface to which these signaling substances bind. If the lymphoma cells receive
the signal via their CCR7 receptor, they migrate into the lymph nodes and into
specific areas within the spleen.


CCR7 not
only mediates the migration of the lymphoma cells, it is also apparently
crucial for their development and survival. As the two researchers showed in a
next step, the lymphoma cells proliferate in the lymph nodes or in the spleen
very slowly if this receptor is absent.

However, with
the aid of CCR7 the cancer cells find their survival niche in the T-cell zones
of the lymph nodes and the spleen. In these zones T cells are usually made fit
for defense. “It is paradoxical that lymphoma cells as former B cells find an
absolutely optimal microenvironment for their growth in these T-cell zones,”
Dr. Höpken said.

There the
lymphoma cells crosstalk with stromal cells (connective tissue cells), which subsequently
secrete increased quantities of the chemokines CCL19/CCL21. The CCR7 receptor
not only mediates the homing of additional lymphoma cells to the lymph nodes or
spleen, but also stimulates their proliferation.

On the
other hand, the lymphoma cells themselves secrete a signaling substance
(lymphotoxin) which induces the stromal cells to secrete more and more
chemokines. In this way the lymphoma cells ensure their survival. This may also
explain why some lymphomas are so aggressive.

In mice
the researchers succeeded in breaking this vicious cycle. Using an active
substance that blocks the binding of the lymphotoxins to the stromal cells,
they were able to stop tumor growth. “In the future,” Dr. Rehm said, “it may be
that therapeutic strategies will not target the lymphoma cells directly, but
rather the connective tissue so vital for their survival.”

*Cooperative function of CCR7 and lymphotoxin in the formation of a
lymphoma-permissive niche within murine secondary lymphoid organs

Armin Rehm1,2, Angela Mensen1,
Kristina Schradi3, Kerstin Gerlach1, Stefanie Wittstock1,
Susann Winter3,Gilbert Büchner3, Bernd Dörken1,2,
Martin Lipp3, and Uta E. Höpken3

for Molecular Medicine, MDC, Department of Hematology, Oncology and
Tumorimmunology, 13125 Berlin, Germany

Universitätsmedizin Berlin, Department of Hematology and Oncology, Campus
Virchow-Klinikum, 13353 Berlin, Germany

for Molecular Medicine, MDC, Department of Tumor Genetics and Immunogenetics;
13125 Berlin, Germany

Corresponding author: Uta E. Höpken or Armin Rehm, Max-Delbrück-Center
for Molecular Medicine, MDC, 13125 Berlin, Germany, e-mail:; phone : +49-30-94063330; fax: +49-30-94063390;
email:; phone : +49-30-94063229; fax:



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